黑色素瘤转移相关蛋白的差异蛋白质组学研究
摘要
一、研究目的：
以B16F10及其相应肺转移的移植瘤作为研究对象,应用2D-DIGE的方法联合质谱技术鉴定黑色素瘤转移相关的蛋白,并验证部分蛋白的功能,以期为临床上找到预测黑色素瘤血道转移的标志物提供理论依据。
二、研究内容：
1.第一部分的研究内容主要是在小鼠B16F10的皮下移植瘤传代过程中,发现若干小鼠出现自发性肺转移,我们将具有黑色素瘤转移的肺脏进一步移植至小鼠的鼠蹊部,并进行传代,获得了稳定传代的肺转移移植瘤(B16M组),并比较了肺转移移植瘤与B16F10移植瘤(B16组)之间的特性差异。
2.第二部分的研究内容主要是应用差示凝胶电泳技术比较了B16组和B16M组之间的差异蛋白表达,应用质谱技术鉴定了相关蛋白。
3.第三部分的研究内容主要是利用western blotting的方法验证vimentin的质谱结果,并在70例有完整预后的恶性黑色素瘤临床标本上探究其临床意义。
三、研究方法：
1.第一部分：50只C57BL／6J小鼠,雌雄各半分成两组,其中25只C57BL／6J小鼠的鼠蹊部接种B16F10单细胞悬液(B16组),另外25只接种肺转移移植瘤的单细胞悬液(B16M组),待肿瘤直径约为1cm左右时处死小鼠,分离收集肿瘤组织,进行H&E染色。观察H&E切片,计数2组的血管生成拟态密度(VMD)及微血管密度(MVD),进行MMP-2及MMP-9的免疫组织化学染色。
2.第二部分：分别提取8例B16组及8例B16M组冻存肿瘤组织的蛋白,将每组8例的蛋白提取物混合在一起,进行差示凝胶电泳。在同一块胶上分别应用Cy3、Cy5标记各组样本及Cy2标记2组的混合样本作为内参,在第二块胶上进行反向标记,Cy2, Cy3, Cy5的激发波长分别是488/520nm,532/580nm和633/670nm, DeCyder软件进行胶内和胶与胶之间的差异分析,获得的差异表达的蛋白点经基质辅助激光解析电离飞行时间质谱(MALDI-TOF/TOF-MS)分析,获得肽质量指纹图的数据,利用MASCOT Peptide Mass Fingerprint查询软件搜索并鉴定差异蛋白质。
3.第三部分：应用western blotting的方法在上述提取的每组8例的蛋白标本中验证质谱结果,并收集随访完整的临床病例资料,进行免疫组织化学染色来进一步探究差异蛋白的临床意义。
四、研究结果
1.B16M组与B16组的特性差异
B16M组的肿瘤组织外观颜色变浅,呈灰白色或灰黄色,质地呈鱼肉样,B16组的肿瘤组织呈典型的黑色,质地较软。通过H&E染色的观察和MMP-2、MMP-9的免疫组织化学染色,发现B16M中存在血管生成拟态(VM),且VMD较B16组显著增高,MMP-2、MMP-9的阳性表达率也高于后者,且B16M组有明显色素缺失的特征,类似于临床上的无色素黑色素瘤的表现,说明B16M具有高转移高侵袭力的特质。
2.B16M组与B16组的差示凝胶电泳和质谱结果
选择2D-DIGE来替代传统的2-DE筛选转移组与原发组的差异表达蛋白,并应用MALDI-TOF/TOF MS来鉴定差异蛋白点,共获得13个转移相关蛋白,其中11个在B16M组中上调,2个为下调,上调的蛋白有：vimentin、PGK1、enolase 1、TPI、Bip、laminin binding protein、GAPDH、myoglobin、proteasome activator reg alpha、β-actin和γ-actin,下调的为2个未命名蛋白。所示蛋白其功能涉及细胞骨架、糖代谢、分子伴侣和免疫调节等多方面。
3. vimentin的质谱结果验证和临床意义
应用Western Blotting方法验证了质谱中vimentin的鉴定结果,并在70例临床随访完整的标本中应用免疫组化检测vimentin的表达,vimentin的阳性表达为肿瘤细胞胞浆染成黄色,阳性细胞数>40%为高表达组,<=40%为低表达组。采用卡方检验检测vimentin的高／低表达与患者各临床病理资料之间的关系,可见vimentin的高表达与血道转移有密切的联系,而与年龄、性别、发病部位、TNM分期和淋巴结转移之间无明显的联系,P值均大于0.05。
五、研究结论
Vimentin与黑色素瘤的转移密切相关,高表达的vimentin对于原发黑色素瘤来说,是血道转移的预测因素之一。在临床上,Vimentin不仅仅是确诊黑色素瘤的标志物,还是指导临床预后的预测因素之一,有望成为今后预测黑色素瘤血道转移的标志物和治疗的靶点。
Purpose:
2D-DIGE combinding with MALDI-TOF/TOF MS were used to identify the proteins associated with melanoma metastasis. The materials were from transplanted tumors of B16F10 and corresponding lung metastases. And the function of special protein was identified. According to the results, some predictors of melanoma hematogenous metastasis should be found.
Contents:
1. During the passage of B16F10 transplanted tumor subcutaneously, we found some mouse bearing spontaneous lung metastases. We picked out the metastatic spots of the lung, and transplanted them to the mouse groin to be passaged stably. We termed them as B16M group and compared the differential characteristics between it with B16 group, i.e. B16F10 transplanted tumors.
2.2D-DIGE (Two dimensional Differential in Gel Electrophoresis) was used to investigate the differential proteins expression between two groups which were identified by MS (Mass Spectrometry)
3. The MS results of vimentin was validated by western blotting, and its clinical significance was studied in 70 samples with detailed follow-up.
Methods:
1. Fifty C57BL/6J mouse were divided into two groups, one was inoculated B16F10 single cell suspension (B16 group), the other was inoculated single cell suspension of transplanted tumors from lung metastases (B16M group). The mouse were sacrificed when the tumor diameter was up to 1 cm, and the tumor tissures were separated and harvested. VMD and MVD were counted. MMP-2 and MMP-9 immunohistochemical staining were performed in two group samples.
2. To abstract proteins from eight pairs of B16M and B16 tissues, and mix them respectively. One group was labled by Cy3, the other was labled by Cy5, mixture of equal two groups were labled by Cy2 which was as internal control. The second gel were reversed labled. The excitated wave length of Cy2, Cy3 and Cy5 were 488/520nm,532/580nm and 633/670nm. The statistical analysis was used by DeCyder software and differential expressed proteins were identified by MALDI-TOF/TOF-MS.
3. The MS results were validated by western blotting in the same samples. The clinical significance of individual protein was investigated in the patient paraffin tissues with whole follow-up.
Results:
1. The differential characteristics between B16M group and B16 group
The color of B16M tumor tissues was gray-white or gray-yellow, but B16 tumor was black as usual. VM can be observed in the B16M, and VMD counts were higher significantly in it than in B16. The positively expression of MMP-2 and MMP-9 were also incresed in B16M. The H&E manifestation of B16M look like amelanotic melanoma. So we supposed that B16M has stronger metastatic and invasive property.
2.2D-DIGE and MS results of B16M group and B16 group
There were 13 metastasis-associated proteins which were identified by MS,11 of them were up-regulated in the B16M that included vimentin、PGK1、enolase 1、TPI、Bip、laminin binding protein、GAPDH、myoglobin、proteasome activator reg alpha、β-actin and y-actin,2 hypothetical proteins were down-regulated in the B16M. The function of those proteins involved in cytoskeleton、glycolytic enzymes、immunoproteasome assembly and the chaperone family of protein.
3. The validation of MS result of vimentin and its clinical significance
The result of western blotting was coincident with MS. The immunohistochemical staining of vimentin was performed in the patient paraffin tissues with whole follow-up. The positive expression of vimentin is yellow stained in the tumor cell cytoplasm. We recognized positive cells>40% as higher expression group,<=40% as lower expression group reversely. The higher expression of vimentin is correlated with melanoma hematogenous metastasis, but not associated with age、gende、location、TNM stage and lymph node metastasis.
Conclusion:
Vimentin is associated with melanoma hematogenous metastasis. Higher expression of vimentin is a predictor of hematogenous metastasis for primary melanomas. The significance of vimentin clinically is not only the diagnostic marker, but also one of prognostic factor and treatment target for melanoma patients.
以B16F10及其相应肺转移的移植瘤作为研究对象,应用2D-DIGE的方法联合质谱技术鉴定黑色素瘤转移相关的蛋白,并验证部分蛋白的功能,以期为临床上找到预测黑色素瘤血道转移的标志物提供理论依据。
二、研究内容：
1.第一部分的研究内容主要是在小鼠B16F10的皮下移植瘤传代过程中,发现若干小鼠出现自发性肺转移,我们将具有黑色素瘤转移的肺脏进一步移植至小鼠的鼠蹊部,并进行传代,获得了稳定传代的肺转移移植瘤(B16M组),并比较了肺转移移植瘤与B16F10移植瘤(B16组)之间的特性差异。
2.第二部分的研究内容主要是应用差示凝胶电泳技术比较了B16组和B16M组之间的差异蛋白表达,应用质谱技术鉴定了相关蛋白。
3.第三部分的研究内容主要是利用western blotting的方法验证vimentin的质谱结果,并在70例有完整预后的恶性黑色素瘤临床标本上探究其临床意义。
三、研究方法：
1.第一部分：50只C57BL／6J小鼠,雌雄各半分成两组,其中25只C57BL／6J小鼠的鼠蹊部接种B16F10单细胞悬液(B16组),另外25只接种肺转移移植瘤的单细胞悬液(B16M组),待肿瘤直径约为1cm左右时处死小鼠,分离收集肿瘤组织,进行H&E染色。观察H&E切片,计数2组的血管生成拟态密度(VMD)及微血管密度(MVD),进行MMP-2及MMP-9的免疫组织化学染色。
2.第二部分：分别提取8例B16组及8例B16M组冻存肿瘤组织的蛋白,将每组8例的蛋白提取物混合在一起,进行差示凝胶电泳。在同一块胶上分别应用Cy3、Cy5标记各组样本及Cy2标记2组的混合样本作为内参,在第二块胶上进行反向标记,Cy2, Cy3, Cy5的激发波长分别是488/520nm,532/580nm和633/670nm, DeCyder软件进行胶内和胶与胶之间的差异分析,获得的差异表达的蛋白点经基质辅助激光解析电离飞行时间质谱(MALDI-TOF/TOF-MS)分析,获得肽质量指纹图的数据,利用MASCOT Peptide Mass Fingerprint查询软件搜索并鉴定差异蛋白质。
3.第三部分：应用western blotting的方法在上述提取的每组8例的蛋白标本中验证质谱结果,并收集随访完整的临床病例资料,进行免疫组织化学染色来进一步探究差异蛋白的临床意义。
四、研究结果
1.B16M组与B16组的特性差异
B16M组的肿瘤组织外观颜色变浅,呈灰白色或灰黄色,质地呈鱼肉样,B16组的肿瘤组织呈典型的黑色,质地较软。通过H&E染色的观察和MMP-2、MMP-9的免疫组织化学染色,发现B16M中存在血管生成拟态(VM),且VMD较B16组显著增高,MMP-2、MMP-9的阳性表达率也高于后者,且B16M组有明显色素缺失的特征,类似于临床上的无色素黑色素瘤的表现,说明B16M具有高转移高侵袭力的特质。
2.B16M组与B16组的差示凝胶电泳和质谱结果
选择2D-DIGE来替代传统的2-DE筛选转移组与原发组的差异表达蛋白,并应用MALDI-TOF/TOF MS来鉴定差异蛋白点,共获得13个转移相关蛋白,其中11个在B16M组中上调,2个为下调,上调的蛋白有：vimentin、PGK1、enolase 1、TPI、Bip、laminin binding protein、GAPDH、myoglobin、proteasome activator reg alpha、β-actin和γ-actin,下调的为2个未命名蛋白。所示蛋白其功能涉及细胞骨架、糖代谢、分子伴侣和免疫调节等多方面。
3. vimentin的质谱结果验证和临床意义
应用Western Blotting方法验证了质谱中vimentin的鉴定结果,并在70例临床随访完整的标本中应用免疫组化检测vimentin的表达,vimentin的阳性表达为肿瘤细胞胞浆染成黄色,阳性细胞数>40%为高表达组,<=40%为低表达组。采用卡方检验检测vimentin的高／低表达与患者各临床病理资料之间的关系,可见vimentin的高表达与血道转移有密切的联系,而与年龄、性别、发病部位、TNM分期和淋巴结转移之间无明显的联系,P值均大于0.05。
五、研究结论
Vimentin与黑色素瘤的转移密切相关,高表达的vimentin对于原发黑色素瘤来说,是血道转移的预测因素之一。在临床上,Vimentin不仅仅是确诊黑色素瘤的标志物,还是指导临床预后的预测因素之一,有望成为今后预测黑色素瘤血道转移的标志物和治疗的靶点。
Purpose:
2D-DIGE combinding with MALDI-TOF/TOF MS were used to identify the proteins associated with melanoma metastasis. The materials were from transplanted tumors of B16F10 and corresponding lung metastases. And the function of special protein was identified. According to the results, some predictors of melanoma hematogenous metastasis should be found.
Contents:
1. During the passage of B16F10 transplanted tumor subcutaneously, we found some mouse bearing spontaneous lung metastases. We picked out the metastatic spots of the lung, and transplanted them to the mouse groin to be passaged stably. We termed them as B16M group and compared the differential characteristics between it with B16 group, i.e. B16F10 transplanted tumors.
2.2D-DIGE (Two dimensional Differential in Gel Electrophoresis) was used to investigate the differential proteins expression between two groups which were identified by MS (Mass Spectrometry)
3. The MS results of vimentin was validated by western blotting, and its clinical significance was studied in 70 samples with detailed follow-up.
Methods:
1. Fifty C57BL/6J mouse were divided into two groups, one was inoculated B16F10 single cell suspension (B16 group), the other was inoculated single cell suspension of transplanted tumors from lung metastases (B16M group). The mouse were sacrificed when the tumor diameter was up to 1 cm, and the tumor tissures were separated and harvested. VMD and MVD were counted. MMP-2 and MMP-9 immunohistochemical staining were performed in two group samples.
2. To abstract proteins from eight pairs of B16M and B16 tissues, and mix them respectively. One group was labled by Cy3, the other was labled by Cy5, mixture of equal two groups were labled by Cy2 which was as internal control. The second gel were reversed labled. The excitated wave length of Cy2, Cy3 and Cy5 were 488/520nm,532/580nm and 633/670nm. The statistical analysis was used by DeCyder software and differential expressed proteins were identified by MALDI-TOF/TOF-MS.
3. The MS results were validated by western blotting in the same samples. The clinical significance of individual protein was investigated in the patient paraffin tissues with whole follow-up.
Results:
1. The differential characteristics between B16M group and B16 group
The color of B16M tumor tissues was gray-white or gray-yellow, but B16 tumor was black as usual. VM can be observed in the B16M, and VMD counts were higher significantly in it than in B16. The positively expression of MMP-2 and MMP-9 were also incresed in B16M. The H&E manifestation of B16M look like amelanotic melanoma. So we supposed that B16M has stronger metastatic and invasive property.
2.2D-DIGE and MS results of B16M group and B16 group
There were 13 metastasis-associated proteins which were identified by MS,11 of them were up-regulated in the B16M that included vimentin、PGK1、enolase 1、TPI、Bip、laminin binding protein、GAPDH、myoglobin、proteasome activator reg alpha、β-actin and y-actin,2 hypothetical proteins were down-regulated in the B16M. The function of those proteins involved in cytoskeleton、glycolytic enzymes、immunoproteasome assembly and the chaperone family of protein.
3. The validation of MS result of vimentin and its clinical significance
The result of western blotting was coincident with MS. The immunohistochemical staining of vimentin was performed in the patient paraffin tissues with whole follow-up. The positive expression of vimentin is yellow stained in the tumor cell cytoplasm. We recognized positive cells>40% as higher expression group,<=40% as lower expression group reversely. The higher expression of vimentin is correlated with melanoma hematogenous metastasis, but not associated with age、gende、location、TNM stage and lymph node metastasis.
Conclusion:
Vimentin is associated with melanoma hematogenous metastasis. Higher expression of vimentin is a predictor of hematogenous metastasis for primary melanomas. The significance of vimentin clinically is not only the diagnostic marker, but also one of prognostic factor and treatment target for melanoma patients.
引文
[1]American Cancer Society. Cancer Facts & Figures 2009. Atlanta:American Cancer Society; 2009
[2]Jemal A, Devesa SS, Harlge P, et al. Recent trends in cutaneous melanoma incidence among whites in the United States[J]. J Natl Cancer Inst, 2001,93(9):678-683.
[3]Balch CM, Soong SJ, Gershenwaid JE,et al. Prognostic factors analysis of 17600 melanoma patienis:validation of the American Joint Cancer Committee on melanoma staging system[J]. J Clin Oncol,2001,19(16):3622-3634.
[4]Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome[J]. J Natl Cancer Inst,2006, 98(7):472-482.
[5]Nambiar S, Mirmohammadsadegh A, Doroudi R, et al. Signaling networks in cutaneous melanoma metastasis identified by complementary DNA microarrays[J]. Arch Dermatol,2005,141(2):165-173.
[6]Mandruzzato S, Callegaro A, Turcatel G, et al. A gene expression signature associated with survival in metastatic melanoma[J]. J Transl Med,2006, Nov 27,4:50.
[7]Satyamoorthy K, Muyrers J, Meier F, et al. Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication[J]. Oncogene,2001,20(34):4676-4684.
[8]St Croix B, Rago C, Velculescu V, et al. Genes expressed in human tumor endothelium[J]. Science,2000,289(5482):1197-1202.
[9]Gutheil JC, Campbell TN, Pierce PR et al. Targeted antiangiogenic therapy for cancer using Vitaxin:A humanized monoclonal antibody to the integrin alphavbeta3 [J]. Clin Cancer Res,2000,6(8):3056-3061.
[10]Varambally S, Yu J, Laxman B, et al. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression[J]. Cancer Cell,2005, 8(5):393-406.
[11]Gorg A, Weiss W, Dunn M. Current two-dimensional electrophoresis technology for proteomics[J]. Proteomics,2004,4(12):3665-3685.
[12]龙晓辉,莫志宏,张耀洲.基于二维凝胶电泳的蛋白质定量分析技术[J].化学进展,2006,18(4)：474-481.
[13]Huang SK, Darfler MM, Nicholl MB,et al. LC/MS-based quantitative proteomic analysis of paraffin-embedded archival melanomas reveals potential proteomic biomarkers associated with metastasis[J]. PLoS One,2009,4(2):e4430
[14]Rondepierre F, Bouchon B, Papon J, et al. Proteomic studies of B16 lines: involvement of annexin Al in melanoma dissemination[J]. Biochim Biophys Acta, 2009,1794(1):61-9.
[15]Al-Ghoul M, Bruck TB, Lauer-Fields JL,et al. Comparative proteomic analysis of matched primary and metastatic melanoma cell lines[J]. J Proteome Res, 2008,7(9):4107-4018.
[16]Poste G, Doll J, Brown AE,et al. Comparison of the metastatic properties of B16 melanoma clones isolated from cultured cell lines, subcutaneous tumors, and individual lung metastases[J]. Cancer Res,1982,42(7):2770-2778.
[17]Fidler IJ. Tumor heterogeneity and the biology of cancer invasion and metastasis[J]. Cancer Res,1978,38(9):2651-2660.
[18]唐四元,周建华,蒋海鹰等.无色素性恶性黑色素瘤HMB45和S-100蛋白的表达[J].实用预防医学,2003,10(2)：144-145.
[19]Pizzichetta MA,Talamini R, Stanganelli I, et al. Amelanotic/hypomelanotic melanoma:clinical and dermoscopic features[J].Br J Dermatol,2004,150(6): 1117-1124.
[20]Khaled A, Hammami H, Fazaa B,et al. Primary amelanotic anorectal melanoma: an uncommon neoplasia with poor prognosis[J]. Pathologica,2009,101 (3):126-129.
[21]Tanaka N, Mimura M, Kimijima Y,et al. Clinical investigation of amelanotic malignant melanoma in the oral region[J]. J Oral Maxillofac Surg, 2004,62(8):933-937.
[22]Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro:vasculogenic mimicry[J].Am J Pathol,1999, 155(3):739-752.
[23]Bissell MJ. Tumor plasticity allows vasculogenic mimicry, a novel form of angiogenic switch. A rose by any other name[J]. Am J Pathol,1999,155(3):675-679.
[24]Hendrix MJ, Seftor EA, Kirschmann DA,et al. Molecular biology of breast cancer metastasis. Molecular expression of vascular markers by aggressive breast cancer cells[J]. Breast Cancer Res,2000,2(6):417-22.
[25]Sood AK, Seftor EA, Fletcher MS,et al. Molecular determinants of ovarian cancer plasticity[J]. Am J Pathol,2001,158(4):1279-1288.
[26]Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis[J]. Am J Pathol,2000,156(2):361-381.
[27]Seftor EA, Meltzer PS, Schatteman GC, et al. Expression of multiple molecular phenotypes by aggressive melanoma tumor cells:role in vasculogenic mimicry[J]. Crit Rev Oncol Hematol,2002,44(1):17-27.
[28]Sun BC, Zhang SW, Zhao XL, et al.Study on vasculogenic mimicry in malignant melanoma[J]. Zhonghua Bing Li Xue Za Zhi,2003,32(6):539-543.
[29]Chung LW, Huang WC, Sung SY, et al. Stromal-epithelial interaction in prostate cancer progression[J]. Clin Genitourin Cancer,2006,5(2):162-170.
[30]Shirakawa K, Kobayashi H, Sobajima J, et al. Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model [J].Breast Cancer Res,2003,5(3):136-9.
[31]Sun T, Zhao N, Zhao XL,et al. Expression and functional significance of Twistl in hepatocellular carcinoma:its role in vasculogenic mimicry[J]. Hepatology,2010, 51(2):545-556.
[32]Sood AK, Fletcher MS, Zahn CM, et al. The clinical significance of tumor cell-lined vasculature in ovarian carcinoma:implications for anti-vasculogenic therapy[J].Cancer Biol Ther,2002,1(6):661-664.
[33]Sun B, Qie S, Zhang S, et al. Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors[J]. Hum Pathol,2008,39(3):444-451.
[34]Li M, Gu Y, Zhang ZG, et al. Vasculogenic mimicry:a new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res.2009 Dec 17. [Epub ahead of print]
[35]Reynolds T. For proteomics research, a new race has begun[J]. J Natl Cancer Inst,2002,94(8):552-554.
[36]钱小红,贺福初.蛋白质组学：理论与方法[M].北京：科学出版社.2003.
[37]Pandey A, Mann M. Proteomics to study genes and genomes[J]. Nature,2000, 405(11):837-846.
[38]Lilley KS, Friedman DB. All about DIGE:quantification technology for differential-display 2D-gel proteomics [J]. Expert Rev Proteomics,2004,1(4):401-409.
[39]Unlu M, Morgan ME, Minden JS, et al. Difference gel electrophoresis:a single gel method for detecting changes in protein extracts[J]. Electrophoresis,1997,18(11): 2071-2077.
[40]Alban A, David SO, Bjorkesten L,et al. A novel experimental design for comparative two-dimensional gel analysis:two-dimensional difference gel electrophoresis incorporating a pooled internal standard [J]. Proteomics,2003,3(1): 36-44.
[41]Tonge R, Shaw J, Middleton B, et al.Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology [J]. Proteomics,2001,1(3):377-396.
[42]Marouga R, David S, and Hawkins E, et al., The development of the DIGE system:2D fluorescence difference gel analysis technology[J]. Anal Bioanal Chem, 2005,382(3):669-678.
[43]Wu WW, Wang G, Baek SJ, etal. Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2Dgel or LC-MALDI TOF/TOF[J]. J Porteome Res,2006,5(3):651-658.
[44]Maltman DJ, Gadd SM., Simon WJ, et al. Differential proteomic analysis of the endoplasmic reticulum from developing and germinating seeds of castor (Ricinus communis) identifies seed protein precursors as significant components of the endoplasmic reticulum[J]. Proteomics,2007,7(9):1513-1528.
[45]Nordvarg H, Flensburg J, Ronno,et al.A Proteomics approach to the study of absorption, distribution, metabolism, excertion, and toxicity[J]. J Biomol Tech,2004, 15(4):265-275.
[46]Amme S, Matros A, Schlesier B, et al. Proteome analysis of cold stress response in Aabidopsis thaliana using DIGE-technology[J]. J Exp Bot,2006,57 (7): 1537-1546.
[47]Byrne JC, Downes MR, O'Donoghue N,et al.2D-DIGE as a strategy to identify serum markers for the progression of prostate cancer[J]. J Proteome Res, 2009,8(2):942-957.
[48]Katayama M, Nakano H, Ishiuchi A, et al. Protein pattern difference in the colon cancer cell lines examined by two-dimensional differential in-gel electrophoresis and mass spectrometry[J]. Surg Today,2006;36(12):1085-1093.
[49]Yao H, Zhang Z, Xiao Z, et al. Identification of metastasis associated proteins in human lung squamous carcinoma using two-dimensional difference gel electrophoresis and laser capture microdissection[J]. Lung Cancer,2009,65(1):41-48.
[50]Orimo T, Ojima H, Hiraoka N, et al. Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma[J]. Hepatology,2008,48(6):1851-1863.
[51]Warburg O. On the origin of cancer cells[J]. Science,1956,123(3191):309-314.
[52]Gatenby RA, Gillies RJ. Why do cancers have high aerobiogly colysis? [J]. Nat Rev Cancer,2004,4(11):891-899.
[53]Hsu PP, Sabatini DM. Cancer cell metabolosm:Warburg and beyond[J]. Cell, 2008,134(6):703-707.
[54]Ken G. Energy deregulation licensing tumors to grow[J]. Science,2006, 312(5777):1158-1159.
[55]Pelicano H, Martin DS, Xu RH, et al. Glycolysis inhibition for anticancer treatment [J]. Ongene,2006,25?(34):4633-4646.
[56]Chen Z, Lu WQ, Garcia PC, et al. The Warburg effect scancer therapeutic implications[J]. J Bioenerg Biomember,2007,39(3):267-274.
[57]Blake CC, Rice DW. Phosphoglycerate kinase[J]. Philos Trans R Soc Lond B Biol Sci,1981,293(1063):93-104.
[58]Valentin C, Birgens H, Craescu CT, et al. A phosphoglycerate kinase mutant (PGK Herlev; D285V) in a Danish patient with isolated chronic hemolytic anemia: mechanism of mutation and structure-function relationships[J]. Hum Mutat,1998, 12(4):280-287.
[59]Yeh CS, Wang JY, Chung FY, et al. Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers[J]. Oncol Rep, 2008,19(1):81-91.
[60]Hwang TL, Liang Y, Chien KY, et al. Overex-pression and elevated serum levels of phos-phoglycerate kinase 1 in pancreatic ductal adeno-carcinoma[J]. Proteomics,2006,6(7):2259-2272.
[61]Shichijo S, Azuma K, Komatsu N, et al. Two proliferation-related proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+ colon cancer[J]. Clin Cancer Res,2004,10(17):5828-5836.
[62]Chen G, Gharib TG, Wang H, et al. Protein profiles associated with survival in lung adenocarcinoma[J]. Proc Natl Acad Sci U S A,2003,100:(23):13537-13542.
[63]Chuthapisith S, Layfield R, Kerr ID, et al. Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs[J]. Int J Oncol,2007,30(6):1545-1551.
[64]Wang J, Wang J, Dai J, et al. A glycolytic mechanism regulating an angiogenic switch in prostate cancer[J]. Cancer Res,2007,67(1):149-159.
[65]Zieker D, Konigsrainer I, Traub F, et al. PGK1, a potential marker for peritoneal dissemination in gastric cancer[J]. Cell Physiol Biochem,2008,21(5-6):429-436.
[66]Miles L A, Dahlberg C M, Plescia J, et al. Role of cell-surface lysines in plasminogen binding to cells:identification of alpha-enolases as a candidate plasminogen receptor[J]. Biochemistry,1991,30(6):1682-1691.
[67]Nakajima K, Hamanoue M, Takemoto N, et al. Plasminogen binds specifically to a alpha-enolase on rat neuronal plasma membrane[J]. J Neurochem,1994,63(6): 2048-2057.
[68]Pancholi V, Fischetti V A. a-Enolase, a novel strong plasminogen binding protein of the surface of pathogenic streptococci[J]. J Biol Chem,1998,273(23): 14503-14515.
[69]Eriksson B, Oberg K, Stridsberg M, et al. Tumor markers in neuroendocrine tumors[J]. Digestion,2000,62, Suppl 1:33-38.
[70]Niklinski J, Furman M. Clinical tumour markers in lung cancer[J]. Eur J Cancer Prev,1995,4(2):129-138.
[71]Kaiser E, Kuzmits R, Pregant P, et al. Clinical biochemistry of neuron specific enolase[J].Clin Chim Acta,1989,183(1):13-31.
[72]Takashima M, Kuramitsu Y, Yokoyama Y,et al.Overexpression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma:Association with tumor progression as determined by proteomic analysis[J]. Proteomics,2005,5(6):1686-1692.
[73]He P, Naka T, Serada S,et al. Blackwell Publishing Asia Proteomics-based identification of a-enolase as a tumor antigen in non-small lung cancer[J]. Cancer Sci, 2007; 98(8):1234-1240.
[74]Kassie F, Anderson LB, Higgins L,et al. Chemopreventive agents modulate the protein expression profile of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo[a]pyrene-induced lung tumors in A/J mice [J]. Carcinogenesis,2008, 29(3):610-619.
[75]Chen G, Gharib TG, Huang CC, et al. Proteomic analysis of lung adenocarcinoma:identification of a highly expressed set of proteins in tumors[J]. Clin Cancer Res,2002,8(7):2298-2305.
[76]Kuramitsu Y, Nakamura K. Proteomic analysis of cancer tissues:shedding light on carcinogenesis and possible biomarkers[J]. Proteomics,2006,6(20):5650-5661.
[77]Huang ZY, Xiong G, Zhang J,et al. Screening of differentially expressed proteins from human esophageal cancer and esophageal tissues by two-dimensional difference gel electrophoresis and mass spectrometry[J]. Nan Fang Yi Ke Da Xue Xue Bao, 2007,27(9):1406-1409.
[78]Ayscough K R. In vivo functions of actin-binding proteins[J].Curr Opin Cell Biol, 1998,10(1):102-111.
[79]Otey C A, Kalnoski M H, Bulinski JC. Identification and quantification of actin isoforms in vertebrate cells and tissues[J]. J Cell Biochem,1987,34(2):113-124.
[80]Chou CC, Davis RC, Fuller ML,et al. Gamma-Actin:Unusual mRNA 3'-untranslated sequence conservation and amino acid substitutions that may be cancer related[J]. Proc Natl Acad Sci,1987,84(9):2575-2579.
[81]Sanju'an X, Fern'andez P L, Miquel R. et al. Overexpression of the 67-kD laminin receptor correlates with tumour progression in human coloreactal carcinoma[J]. J Pathol,1996,179(4):376-380.
[82]De Manzoni G, Guglielmi A, Verlato G, et al. Prognostic significance of 67-kDa laminin receptor expression in advanced gastric cancer[J]. Oncology,1998,55(5): 456-460.
[83]Lee WA, Kim WH, Kim YI, et al. Overexpression of the 67 kD laminin receptor correlates with the progression of gastric carcinoma[J]. Pathol Res Pract, 1996,192(12):1195-1201.
[84]Rajagopal S, Moskal T L, Wang H, et al. Efficacy and specificity of antisense laminin cahin-specific expression vestors in blocking laminin-induction by TGFβ1: effect of laminin blockade on TGF β 1-mediated cellular responses[J]. J Cell Physiol, 1999,178(3):296-303.
[85]Vollmers HP, Imhof BA, Braun S, et al. Monoclonal antibodies which prevent experimental lung metastases:interference with adhesion of tumour cells to laminin[J]. FEBS Lett,1984,172(1):17-20.
[86]Trombetta ES, Parodi AJ. Quality control and protein folding in the secretory pathway[J]. Annu Rev Cell Dev Biol,2003,19:649-76
[87]Dong D, Dubeau L, Bading J, et al. Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors[J]. Hum Gene Ther,2004,15 (6):553-561.
[88]Misra UK, Deedwania R, Pizzo SV. Activation and crosstalk between Akt, NF-κ B, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78[J]. J Biol Chem,2006,281 (19):13694-136707.
[89]Knowlton JR, Jolnston SC, Whitby FG, et al. Structure of the proteasome activator REGalpha (PA28alpha) [J]. Nature,1997,390(6660):639-643.
[90]李洁,谢文光,沈备奋等.GAPDH功能多样性研究进展[J].军事医学科学院院刊,2006,30(5)：483—486.
[91]Merx MW, Flogel U, Stumpe T, et al. Myoglobin facilitates oxygen diffusion[J]. FASEB J,2001,15(6):1077-9.
[92]Galluzzo M, Pennacchietti S, Rosano S, et al. Prevention of hypoxia by myoglobin expression in human tumor cells promotes differentiation and inhibits metastasis[J]. J Clin Invest,2009,119(4):865-875.
[93]Nieminen M, Henttinen T, Merinen M, et al. Vimentin function in lymphocyte adhesion and transcellular migration[J]. Nat Cell Biol,2006,8 (2):156-162.
[94]Colucci-Guyon E, Portier MM, Dunia I, et al. Mice lacking vimentin develop and reproduce without an obvious phenotype[J]. Cell,1994,79(4):679-694.
[95]Eckes B, Colucci-Guyon E, Smola H, et al.Impaired wound healing in embryonic and adult mice lacking vimentin[J]. J Cell Sci,2000,113 (Pt 13):2455-2462.
[96]Brakebusch C, Fassler R, The integrin-actin connection, an eternal love affair[J]. EMBO J,2003,22 (10):2324-2333.
[97]Calderwood DA. Integrin activation[J]. J Cell Sci,2004,117 (Pt5):657-666.
[98]van der Neut R, Krimpenfort P, Calafat J,et al. Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice[J]. Nat Genet,1996,13 (3):366-369.
[99]Gonzales M, Weksler B, Tsuruta D, et al. Structure and function of a vimentin-associated matrix adhesion in endothelial cells[J]. Mol Biol Cell,2001,12 (1):85-100.
[100]Tsuruta D,Jones JC. The vimentin cytoskeleton regulates focal contact size and adhesion of endothelial cells subjected to shear stress[J]. J Cell Sci,2003,116 (Pt24): 4977-4984.
[101]Bershadsky AD, Tint IS, Svitkina TM. Association of intermediate filaments with vinculin-containing adhesion plaques of fibroblasts[J]. Cell Motil Cytoskelet, 1987,8 (3):274-283.
[102]Esue O, Carson AA, Tseng Y, et al. A direct interaction between actin and vimentin filaments mediated by the tail domain of vimentin[J]. J Biol Chem,2006, 281 (41):30393-30399.
[103]Willipinski-Stapelfeldt B, Riethdorf S, Assmann V,et al. Change in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells[J]. Clin Cancer Res,2005,11(22),8006-8014.
[104]Hu L,Lau SH, Tzang CH, et al. Association of Vimentin overexpression and hepatocellular carcinoma metastasis[J]. Oncogene,2004,23(1):298-302.
[105]Chen YR, Juan HF, Huang HC, et al. Quantitative proteomic and genomic profiling reveals metastasis-related protein expression patterns in gastric cancer cells[J]. J Proteome Res,2006,5(10):2727-2742.
[106]Alonso SR, Tracey L, Ortiz P, et al. A High-Throughput Study in Melanoma Identifies Epithel ial-Mesenchymal Transition as a Major Determinant of Metastasis[J]. Cancer Res,2007,67(7):3450-3460.
[107]Wei J, Xu G, Zhang Y, et al. Overexpression of vimentin contributes to prostate cancer invasion and metastasis via src regulation[J]. Anticancer Res,2008,28(1 A): 327-334.
[108]Wu M,Bai X, Xu G, et al. Proteome analysis of human androgen-independent prostate cancer cell lines:Variable metastatic potentials correlated with vimentin expression[J].Proteomics,2007,7(12):1973-1983.
[109]Hendrix MJ, Seftor EA, Chu YW, et al. Coexpression of vimentin and keratins by human melanoma tumor cells correlation with invasive and metastatic potential[J]. J Natl Cancer Inst,1992,84(3):165-174.
[110]Ben-Ze'ev A, Raz A. Relationship between the organization and synthesis of vimentin and the metastatic capability of B16 melanoma cells[J]. Cancer Res, 1985,45(6):2632-2641.
[1]Jenul A, Siegcl R, Ward E, el al. Cancer statistics[J]. CA Cancer J Clin,2006, 56(3):106-130.
[2]Jemal A, Devesa SS, Harlge P, et al. Recent trends in cutaneous melanoma incidence among whites in the United States[J]. J Nati Cancer Insi,2001,93(9): 678-683.
[3]Goldstein AM, Tucker MA. Etiology, epidemiology, risk factors, and public health issues of melanoma[J]. Curr Opin Oncol,1993,5(2):358-363.
[4]Ries LA. Wiiigo PA. Miller DS, et al. The annual report of the nation on the status of cancer,1973-1997, with a special section on colorectal cancer[J]. Cancer,2000, 88(10):2398-2424.
[5]Stevens NG, LiffJ M, Weiss NS. Plantiu melanoma:is the incidence of melanoma of the sole of the fool really higher in blacks than whites? [J]. Int J Cancer,1990, 45(4):691-693.
[6]Clark WH, Tucker MA, Janipel RM. Atypical melanocytie nevi of the genital type with a discussion of reciprocal parenchymal-stromal intendtions in the biology of neoplasia[J]. Hum Pathol,1998:29(1. suppl 1):S1-S24.
[7]McNutt NS, Urmacher C, Hakimian J, et al. Malignant melanoma:morphologic patterns and immunohistochemical reactivity[J]. J Cutan Pathol,1995,22(6): 502-517.
[8]Crowson AN, Magro CM, Milim MC. The Melanocytic Proliferations: A Comprehensive Textbook of Pigmental lesions[M]. New York. NY:Wiley-Liss, 2001:539.
[9]Fiotte TJ, Mibm MC. Lentigo maligna and malignant melanoma in situ, lentigo maligna type[J]. Hum Pathol,1999,30(5):533-536.
[10]Tannous ZS, Lemer LH, Duncan LM, et al. Progression to invasive melanoma from malignant melanoma in situ. Lentigo maligna type[J]. Hum Pathol,2000,31(6):705-708.
[11]Anderson WF, Pfeiffer RM, Tucker MA, et al. Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma. Cancer, 2009,115(18):4176-4185.
[12]Lachiewicz AM, Berwick M, Wiggins CL, et al. Epidemiologic support for melanoma heterogeneity using the surveillance, epidemiology, and end results program[J]. J Invest Dermatol,2008,128(5):1340-1342.
[13]Bradford PT, Goldstein AM, McMaster ML, et al. Acral lentiginous melanoma: incidence and survival patterns in theUnitedStates,1986-2005[J]. Arch Dermatol, 2009,145(4):427-434.
[14]Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma:I. Common and atypical naevi[J]. Eur J Cancer,2005, 41(1):28-44.
[15]Olsen CM, Zens MS, Stukel TA, et al. Nevus density and melanoma risk in women:a pooled analysis to test the divergent pathway hypothesis[J]. Int J Cancer, 2009,124(4):937-944.
[16]Chang YM, Newton-Bishop JA, Bishop DT, et al. A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes[J]. Int J Cancer,2009,124(2):420-428.
[17]Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma[J]. JAMA,1997,277(18):1439-1444.
[18]IARCIn:IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Solar and Ultraviolet Radiation, vol.55. Lyon (France):IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; 1992.
[19]Yu CL, Li Y, Freedman DM, et al. Assessment of lifetime cumulative sun exposure using a self-administered questionnaire:reliability of two approaches[J]. Cancer Epidemiol Biomarkers Prev,2009,18(2):464-471.
[20]Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma:Ⅱ. Sun exposure[J]. Eur J Cancer,2005,41(1):45-60.
[21]Rutter JL, Bromley CM, Goldstein AM, et al. Heterogeneity of risk for melanoma and pancreatic and digestive malignancies:a melanoma case-control study[J]. Cancer,2004,101(12):2809-16.
[22]Goldstein AM, Chan M, Harland M, et al. Features associated with germline CDKN2A mutations:a GenoMEL study of melanoma-prone families from three continents[J]. J Med Genet,2007,44(2):99-106.
[23]Goldstein AM, Chan M, Harland M, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL[J]. Cancer Res,2006,66(20):9818-9828.
[24]Goldstein AM, Landi MT, Tsang S, et al. Association of MCI R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations[J]. Cancer Epidemiol Biomarkers Prev,2005,14(9):2208-2212.
[25]Clark WH, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin[J]. Cancer RES,1969, 29(3):705-727.
[26]Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma[J]. ANN Surg,1970,172(5):902-908.
[27]Balch CM, Soong SJ, Gershenwaid JE,et al. Prognostic factors analysis of 17600 melanoma patienis:validation of the American Joint Committee on Cancer melanoma staging system[J]. J Clin Oncol,2001,19(16):3622-3634.
[28]Balch CM, Buaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer siaging system for cutaneous melanoma[J]. J Clin Oncol,2001,19(16):3635-3648.
[29]Balch CM, Btizaid AC, Soong SJ, et al. New TNM melanoma staging system:linking biology and natural history to clinical outcomes[J]. Semin Surg oncol,2003,21(1):43-52.
[30]Yan S, Brennick JB. False-positive rate of immunoperoxidase stains for MARTI/Melan A in lymph nodes[J]. Am J Surg Pathol,2004,28(5):596-600.
[31]Elder DE, Guerry D, Epstein MN, et al. Invasive malignant melanomas lacking competence for metastasis[J]. Am J Dermatopathol,1984:6(suppl):55-61.
[32]Guerry D, Synnestvedt M, Elder DE, et al. lessons from tumor progression:the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent[J]. J Invest Dermatol,1993,100(3):342S-345S.
[33]Barnhill RL, Katzen J, Spatz A, et al. The importance of Mitotic rate as a prognostic factor for localized cutaneous melanoma[J]. J Cutan Pathol,2005, 32(4):268-273.
[34]Azzola MF, Shaw HM, Thompson JF, et al. Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma:an analysis of 3661 patients from a single center[J]. Cancer,2003, 97(6):1488-1498.
[35]Gimotty PA, Guerry D,Ming ME, et al. Thin primary cutaneous malignant melanoma:a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging[J]. J Clin Oncol,2004,22(18): 3668-3676.
[36]Guitart J, Lowe L, Piepkom M, et al. Histological characteristics of metastasizing thin melanomas:a case-control study of 43 cases[J]. Arch Dermatol, 2002,138(5):603-608.
[37]Slingluff CL, Vollmer RT, Reintgen DS, et al. Lethal "thin" malignant melanoma:identifying patients at risk[J]. Ann Surg,1988,208(2):150-161.
[38]Clemente CG, Mihm MC, Bufalina R, et al. Prognoslic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma[J]. Cancer,1996,77(7):1303-1310.
[39]Elder DE, Guerry D, VanHom M, et al. The role of lymph node dissection for clinical stage malignant melanoma of intermediate thickness (1.51-3.99 mm) [J]. Cancer,1985,56(2):413-418.
[40]Mraz-Gemhard S, Sagebiel RW, Kashani-Sabet M, et al. Prediction of sentinel lymph node micro metastasis by histological features in primary cutaneous malignant melanoma[J]. Arch Dermatol,1998,134(8):983-987.
[41]Bamliill R, Dy K, Lugassy C, et al. Angiotropism in cutaneous melanoma:a prognostic factor strongly predicting risk for metastasis[J]. J Invest Dermatol,2002, 119(3):705-706.
[42]Miller AJ, Mihm MC. Melanoma[J]. N Engl J Med,2006,355(1):51-65.
[43]DeRisi J, Penland L, Brown PO, et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer[J]. Nat Genet,1996,14(4):457-460.
[44]Ryu B, Kim DS, DeLuca AM, et al. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression[J]. PLoS ONE,2007,2(7):e594.
[45]Hoek K, Rimm DL, Williams KR, et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas[J]. Cancer Res,2004, 64(15):5270-5282.
[46]Smith AP, Hoek K, Becker D. Whole-genome expression profiling of the melanoma progression pathway reveals marked molecular differences between nevi/melanoma in situ and advanced-stage melanomas[J]. Cancer Biol Ther,2005, 4(9):1018-1029.
[47]Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome[J]. J Natl Cancer Inst,2006, 98(7):472-482.
[48]Nambiar S, Mirmohammadsadegh A, Doroudi R, et al. Signaling networks in cutaneous melanoma metastasis identified by complementary DNA microarrays[J]. Arch Dermatol,2005,141 (2):165-173.
[49]Mandruzzato S, Callegaro A, Turcatel G, et al. A gene expression signature associated with survival in metastatic melanoma[J]. J Transl Med,2006, Nov 27, 4:50.
[50]Seftor EA, Brown KM, Chin L, et al. Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment[J]. Cancer Res,2005, 65(22):10164-10169.
[51]Feinberg AP. Phenotypic plasticity and the epigenetics of human disease[J]. Nature,2007,447(7143):433-440.
[52]Muthusamy V, Duraisamy S, Bradbury CM, et al. Epigenetic silencing of novel tumor suppressors in malignant melanoma[J]. Cancer Res,2006,66(23): 11187-11193.
[53]Hoon DS, Spugnardi M, Kuo C, et al. Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients[J]. Oncogene,2004,23(22):4014-4022.
[54]Furuta J, Nobeyama Y, Umebayashi Y, et al. Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas[J]. Cancer Res,2006,66(12):6080-6086.
[55]Spugnardi M, Tommasi S, Dammann R, et al. Epigenetic inactivation of RAS association domain family protein 1 (RASSF1A) in malignant cutaneous melanoma[J]. Cancer Res,2003,63(7):1639-1643.
[56]Worm J, Christensen C, Grφnbaek K, et al. Genetic and epigenetic alterations of the APC gene in malignant melanoma[J]. Oncogene,2004,23(3):5215-5226.
[57]Worm J, Bartkova J, Kirkin AF, et al. Aberrant p27Kipl promoter methylation in malignant melanoma[J]. Oncogene,2000,19(44):5111-5115.
[58]Gonzalgo ML, Bender CM, You EH, et al. Low frequency of p16/CDKN2A methylation in sporadic melanoma:comparative approaches for methylation analysis of primary tumors[J]. Cancer Res,1997,57(23):5336-5347.
[59]Muthusamy V, Duraisamy S, Bradbury CM, et al. Epigenetic silencing of novel tumor suppressors in malignant melanoma[J]. Cancer Res,2006,66(23): 11187-11193.
[60]Hellebrekers DM, Melotte V, Vire E, et al. Identification of epigenetically silenced genes in tumor endothelial cells[J]. Cancer Res,2007,67(9):4138-4148.
[61]Rothhammer T, Bosserhoff AK. Epigenetic events in malignant melanoma[J]. Pigment Cell Res,2007,20(2):92-111.
[62]Hoek K, Rimm DL, Williams KR., et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas[J]. Cancer Res,2004, 64(15):5270-5282.
[63]Bittner M, Meltzer P, Chen Y, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling[J]. Nature,2000,406 (6795):536-540.
[64]Haqq C, Nosrati M, Sudilovsky D, et al. The gene expression signatures of melanoma progression[J]. Proc Natl Acad Sci,2005,102(17):6092-6097.
[65]Seykora JT,. Elenitsas DR,. Horng WH, et al. Gene expression profiling of melanocytic lesions[J]. Am J Dermatopathol,2003,25(1):6-11.
[66]Halaban R, Miglarese MR, Smicun Y, et al. Melanomas, from cell cycle point of view[J]. Int J Mol Med,1998,1(2):419-425.
[67]Bachmann IM, Straume O, Puntervoll HE, et al. Importance of P-cadherin, beta-catenin and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma[J]. Clin Cancer Res,2005,11(24pt1):8606-8614.
[68]Satyamoorthy K, Muyrers J, Meier F, et al. Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication[J]. Oncogene,2001,20(34):4676-4684.
[69]St Croix B, Rago C, Velculescu V, et al. Genes expressed in human tumor endothelium[J]. Science,2000,289(5482):1197-1202.
[70]Gutheil JC, Campbell TN, Pierce PR et al. Targeted antiangiogenic therapy for cancer using Vitaxin:A humanized monoclonal antibody to the integrin alphavbeta3 [J]. Clin Cancer Res,2000,6(8):3056-3061.
[71]Pandey A, Mann M. Proteomics to study genes and genomes[J]. Nature,2000, 405(11):837-846.
[72]Gorg A, Weiss W, Dunn M. Current two-dimensional electrophoresis technology for proteomics[J]. Proteomics,2004,4(12):3665-3685.
[73]Cargile BJ, Sevinsky JR, Essader AS. Immobilized pH gradient isoelectric focusing as a first dimension separation in shotgun proteomics[J]. J Biomol Tech, 2005,16(3):181-189.
[74]龙晓辉,莫志宏,张耀洲.基于二维凝胶电泳的蛋白质定量分析技术[J].化学进展,2006,18(4)：474-481.
[75]Huang SK, Darfler MM, Nicholl MB,et al. LC/MS-based quantitative proteomic analysis of paraffin-embedded archival melanomas reveals potential proteomic biomarkers associated with metastasis[J]. PLoS One,2009,4(2):e4430
[76]Rondepierre F, Bouchon B, Papon J, et al. Proteomic studies of B16 lines: involvement of annexin A1 in melanoma dissemination[J]. Biochim Biophys Acta, 2009,1794(1):61-9。
[77]Al-Ghoul M, Bruck TB, Lauer-Fields JL,et al. Comparative proteomic analysis of matched primary and metastatic melanoma cell lines[J]. J Proteome Res, 2008,7(9):4107-4018.
[2]Jemal A, Devesa SS, Harlge P, et al. Recent trends in cutaneous melanoma incidence among whites in the United States[J]. J Natl Cancer Inst, 2001,93(9):678-683.
[3]Balch CM, Soong SJ, Gershenwaid JE,et al. Prognostic factors analysis of 17600 melanoma patienis:validation of the American Joint Cancer Committee on melanoma staging system[J]. J Clin Oncol,2001,19(16):3622-3634.
[4]Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome[J]. J Natl Cancer Inst,2006, 98(7):472-482.
[5]Nambiar S, Mirmohammadsadegh A, Doroudi R, et al. Signaling networks in cutaneous melanoma metastasis identified by complementary DNA microarrays[J]. Arch Dermatol,2005,141(2):165-173.
[6]Mandruzzato S, Callegaro A, Turcatel G, et al. A gene expression signature associated with survival in metastatic melanoma[J]. J Transl Med,2006, Nov 27,4:50.
[7]Satyamoorthy K, Muyrers J, Meier F, et al. Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication[J]. Oncogene,2001,20(34):4676-4684.
[8]St Croix B, Rago C, Velculescu V, et al. Genes expressed in human tumor endothelium[J]. Science,2000,289(5482):1197-1202.
[9]Gutheil JC, Campbell TN, Pierce PR et al. Targeted antiangiogenic therapy for cancer using Vitaxin:A humanized monoclonal antibody to the integrin alphavbeta3 [J]. Clin Cancer Res,2000,6(8):3056-3061.
[10]Varambally S, Yu J, Laxman B, et al. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression[J]. Cancer Cell,2005, 8(5):393-406.
[11]Gorg A, Weiss W, Dunn M. Current two-dimensional electrophoresis technology for proteomics[J]. Proteomics,2004,4(12):3665-3685.
[12]龙晓辉,莫志宏,张耀洲.基于二维凝胶电泳的蛋白质定量分析技术[J].化学进展,2006,18(4)：474-481.
[13]Huang SK, Darfler MM, Nicholl MB,et al. LC/MS-based quantitative proteomic analysis of paraffin-embedded archival melanomas reveals potential proteomic biomarkers associated with metastasis[J]. PLoS One,2009,4(2):e4430
[14]Rondepierre F, Bouchon B, Papon J, et al. Proteomic studies of B16 lines: involvement of annexin Al in melanoma dissemination[J]. Biochim Biophys Acta, 2009,1794(1):61-9.
[15]Al-Ghoul M, Bruck TB, Lauer-Fields JL,et al. Comparative proteomic analysis of matched primary and metastatic melanoma cell lines[J]. J Proteome Res, 2008,7(9):4107-4018.
[16]Poste G, Doll J, Brown AE,et al. Comparison of the metastatic properties of B16 melanoma clones isolated from cultured cell lines, subcutaneous tumors, and individual lung metastases[J]. Cancer Res,1982,42(7):2770-2778.
[17]Fidler IJ. Tumor heterogeneity and the biology of cancer invasion and metastasis[J]. Cancer Res,1978,38(9):2651-2660.
[18]唐四元,周建华,蒋海鹰等.无色素性恶性黑色素瘤HMB45和S-100蛋白的表达[J].实用预防医学,2003,10(2)：144-145.
[19]Pizzichetta MA,Talamini R, Stanganelli I, et al. Amelanotic/hypomelanotic melanoma:clinical and dermoscopic features[J].Br J Dermatol,2004,150(6): 1117-1124.
[20]Khaled A, Hammami H, Fazaa B,et al. Primary amelanotic anorectal melanoma: an uncommon neoplasia with poor prognosis[J]. Pathologica,2009,101 (3):126-129.
[21]Tanaka N, Mimura M, Kimijima Y,et al. Clinical investigation of amelanotic malignant melanoma in the oral region[J]. J Oral Maxillofac Surg, 2004,62(8):933-937.
[22]Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro:vasculogenic mimicry[J].Am J Pathol,1999, 155(3):739-752.
[23]Bissell MJ. Tumor plasticity allows vasculogenic mimicry, a novel form of angiogenic switch. A rose by any other name[J]. Am J Pathol,1999,155(3):675-679.
[24]Hendrix MJ, Seftor EA, Kirschmann DA,et al. Molecular biology of breast cancer metastasis. Molecular expression of vascular markers by aggressive breast cancer cells[J]. Breast Cancer Res,2000,2(6):417-22.
[25]Sood AK, Seftor EA, Fletcher MS,et al. Molecular determinants of ovarian cancer plasticity[J]. Am J Pathol,2001,158(4):1279-1288.
[26]Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis[J]. Am J Pathol,2000,156(2):361-381.
[27]Seftor EA, Meltzer PS, Schatteman GC, et al. Expression of multiple molecular phenotypes by aggressive melanoma tumor cells:role in vasculogenic mimicry[J]. Crit Rev Oncol Hematol,2002,44(1):17-27.
[28]Sun BC, Zhang SW, Zhao XL, et al.Study on vasculogenic mimicry in malignant melanoma[J]. Zhonghua Bing Li Xue Za Zhi,2003,32(6):539-543.
[29]Chung LW, Huang WC, Sung SY, et al. Stromal-epithelial interaction in prostate cancer progression[J]. Clin Genitourin Cancer,2006,5(2):162-170.
[30]Shirakawa K, Kobayashi H, Sobajima J, et al. Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model [J].Breast Cancer Res,2003,5(3):136-9.
[31]Sun T, Zhao N, Zhao XL,et al. Expression and functional significance of Twistl in hepatocellular carcinoma:its role in vasculogenic mimicry[J]. Hepatology,2010, 51(2):545-556.
[32]Sood AK, Fletcher MS, Zahn CM, et al. The clinical significance of tumor cell-lined vasculature in ovarian carcinoma:implications for anti-vasculogenic therapy[J].Cancer Biol Ther,2002,1(6):661-664.
[33]Sun B, Qie S, Zhang S, et al. Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors[J]. Hum Pathol,2008,39(3):444-451.
[34]Li M, Gu Y, Zhang ZG, et al. Vasculogenic mimicry:a new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res.2009 Dec 17. [Epub ahead of print]
[35]Reynolds T. For proteomics research, a new race has begun[J]. J Natl Cancer Inst,2002,94(8):552-554.
[36]钱小红,贺福初.蛋白质组学：理论与方法[M].北京：科学出版社.2003.
[37]Pandey A, Mann M. Proteomics to study genes and genomes[J]. Nature,2000, 405(11):837-846.
[38]Lilley KS, Friedman DB. All about DIGE:quantification technology for differential-display 2D-gel proteomics [J]. Expert Rev Proteomics,2004,1(4):401-409.
[39]Unlu M, Morgan ME, Minden JS, et al. Difference gel electrophoresis:a single gel method for detecting changes in protein extracts[J]. Electrophoresis,1997,18(11): 2071-2077.
[40]Alban A, David SO, Bjorkesten L,et al. A novel experimental design for comparative two-dimensional gel analysis:two-dimensional difference gel electrophoresis incorporating a pooled internal standard [J]. Proteomics,2003,3(1): 36-44.
[41]Tonge R, Shaw J, Middleton B, et al.Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology [J]. Proteomics,2001,1(3):377-396.
[42]Marouga R, David S, and Hawkins E, et al., The development of the DIGE system:2D fluorescence difference gel analysis technology[J]. Anal Bioanal Chem, 2005,382(3):669-678.
[43]Wu WW, Wang G, Baek SJ, etal. Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2Dgel or LC-MALDI TOF/TOF[J]. J Porteome Res,2006,5(3):651-658.
[44]Maltman DJ, Gadd SM., Simon WJ, et al. Differential proteomic analysis of the endoplasmic reticulum from developing and germinating seeds of castor (Ricinus communis) identifies seed protein precursors as significant components of the endoplasmic reticulum[J]. Proteomics,2007,7(9):1513-1528.
[45]Nordvarg H, Flensburg J, Ronno,et al.A Proteomics approach to the study of absorption, distribution, metabolism, excertion, and toxicity[J]. J Biomol Tech,2004, 15(4):265-275.
[46]Amme S, Matros A, Schlesier B, et al. Proteome analysis of cold stress response in Aabidopsis thaliana using DIGE-technology[J]. J Exp Bot,2006,57 (7): 1537-1546.
[47]Byrne JC, Downes MR, O'Donoghue N,et al.2D-DIGE as a strategy to identify serum markers for the progression of prostate cancer[J]. J Proteome Res, 2009,8(2):942-957.
[48]Katayama M, Nakano H, Ishiuchi A, et al. Protein pattern difference in the colon cancer cell lines examined by two-dimensional differential in-gel electrophoresis and mass spectrometry[J]. Surg Today,2006;36(12):1085-1093.
[49]Yao H, Zhang Z, Xiao Z, et al. Identification of metastasis associated proteins in human lung squamous carcinoma using two-dimensional difference gel electrophoresis and laser capture microdissection[J]. Lung Cancer,2009,65(1):41-48.
[50]Orimo T, Ojima H, Hiraoka N, et al. Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma[J]. Hepatology,2008,48(6):1851-1863.
[51]Warburg O. On the origin of cancer cells[J]. Science,1956,123(3191):309-314.
[52]Gatenby RA, Gillies RJ. Why do cancers have high aerobiogly colysis? [J]. Nat Rev Cancer,2004,4(11):891-899.
[53]Hsu PP, Sabatini DM. Cancer cell metabolosm:Warburg and beyond[J]. Cell, 2008,134(6):703-707.
[54]Ken G. Energy deregulation licensing tumors to grow[J]. Science,2006, 312(5777):1158-1159.
[55]Pelicano H, Martin DS, Xu RH, et al. Glycolysis inhibition for anticancer treatment [J]. Ongene,2006,25?(34):4633-4646.
[56]Chen Z, Lu WQ, Garcia PC, et al. The Warburg effect scancer therapeutic implications[J]. J Bioenerg Biomember,2007,39(3):267-274.
[57]Blake CC, Rice DW. Phosphoglycerate kinase[J]. Philos Trans R Soc Lond B Biol Sci,1981,293(1063):93-104.
[58]Valentin C, Birgens H, Craescu CT, et al. A phosphoglycerate kinase mutant (PGK Herlev; D285V) in a Danish patient with isolated chronic hemolytic anemia: mechanism of mutation and structure-function relationships[J]. Hum Mutat,1998, 12(4):280-287.
[59]Yeh CS, Wang JY, Chung FY, et al. Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers[J]. Oncol Rep, 2008,19(1):81-91.
[60]Hwang TL, Liang Y, Chien KY, et al. Overex-pression and elevated serum levels of phos-phoglycerate kinase 1 in pancreatic ductal adeno-carcinoma[J]. Proteomics,2006,6(7):2259-2272.
[61]Shichijo S, Azuma K, Komatsu N, et al. Two proliferation-related proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+ colon cancer[J]. Clin Cancer Res,2004,10(17):5828-5836.
[62]Chen G, Gharib TG, Wang H, et al. Protein profiles associated with survival in lung adenocarcinoma[J]. Proc Natl Acad Sci U S A,2003,100:(23):13537-13542.
[63]Chuthapisith S, Layfield R, Kerr ID, et al. Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs[J]. Int J Oncol,2007,30(6):1545-1551.
[64]Wang J, Wang J, Dai J, et al. A glycolytic mechanism regulating an angiogenic switch in prostate cancer[J]. Cancer Res,2007,67(1):149-159.
[65]Zieker D, Konigsrainer I, Traub F, et al. PGK1, a potential marker for peritoneal dissemination in gastric cancer[J]. Cell Physiol Biochem,2008,21(5-6):429-436.
[66]Miles L A, Dahlberg C M, Plescia J, et al. Role of cell-surface lysines in plasminogen binding to cells:identification of alpha-enolases as a candidate plasminogen receptor[J]. Biochemistry,1991,30(6):1682-1691.
[67]Nakajima K, Hamanoue M, Takemoto N, et al. Plasminogen binds specifically to a alpha-enolase on rat neuronal plasma membrane[J]. J Neurochem,1994,63(6): 2048-2057.
[68]Pancholi V, Fischetti V A. a-Enolase, a novel strong plasminogen binding protein of the surface of pathogenic streptococci[J]. J Biol Chem,1998,273(23): 14503-14515.
[69]Eriksson B, Oberg K, Stridsberg M, et al. Tumor markers in neuroendocrine tumors[J]. Digestion,2000,62, Suppl 1:33-38.
[70]Niklinski J, Furman M. Clinical tumour markers in lung cancer[J]. Eur J Cancer Prev,1995,4(2):129-138.
[71]Kaiser E, Kuzmits R, Pregant P, et al. Clinical biochemistry of neuron specific enolase[J].Clin Chim Acta,1989,183(1):13-31.
[72]Takashima M, Kuramitsu Y, Yokoyama Y,et al.Overexpression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma:Association with tumor progression as determined by proteomic analysis[J]. Proteomics,2005,5(6):1686-1692.
[73]He P, Naka T, Serada S,et al. Blackwell Publishing Asia Proteomics-based identification of a-enolase as a tumor antigen in non-small lung cancer[J]. Cancer Sci, 2007; 98(8):1234-1240.
[74]Kassie F, Anderson LB, Higgins L,et al. Chemopreventive agents modulate the protein expression profile of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo[a]pyrene-induced lung tumors in A/J mice [J]. Carcinogenesis,2008, 29(3):610-619.
[75]Chen G, Gharib TG, Huang CC, et al. Proteomic analysis of lung adenocarcinoma:identification of a highly expressed set of proteins in tumors[J]. Clin Cancer Res,2002,8(7):2298-2305.
[76]Kuramitsu Y, Nakamura K. Proteomic analysis of cancer tissues:shedding light on carcinogenesis and possible biomarkers[J]. Proteomics,2006,6(20):5650-5661.
[77]Huang ZY, Xiong G, Zhang J,et al. Screening of differentially expressed proteins from human esophageal cancer and esophageal tissues by two-dimensional difference gel electrophoresis and mass spectrometry[J]. Nan Fang Yi Ke Da Xue Xue Bao, 2007,27(9):1406-1409.
[78]Ayscough K R. In vivo functions of actin-binding proteins[J].Curr Opin Cell Biol, 1998,10(1):102-111.
[79]Otey C A, Kalnoski M H, Bulinski JC. Identification and quantification of actin isoforms in vertebrate cells and tissues[J]. J Cell Biochem,1987,34(2):113-124.
[80]Chou CC, Davis RC, Fuller ML,et al. Gamma-Actin:Unusual mRNA 3'-untranslated sequence conservation and amino acid substitutions that may be cancer related[J]. Proc Natl Acad Sci,1987,84(9):2575-2579.
[81]Sanju'an X, Fern'andez P L, Miquel R. et al. Overexpression of the 67-kD laminin receptor correlates with tumour progression in human coloreactal carcinoma[J]. J Pathol,1996,179(4):376-380.
[82]De Manzoni G, Guglielmi A, Verlato G, et al. Prognostic significance of 67-kDa laminin receptor expression in advanced gastric cancer[J]. Oncology,1998,55(5): 456-460.
[83]Lee WA, Kim WH, Kim YI, et al. Overexpression of the 67 kD laminin receptor correlates with the progression of gastric carcinoma[J]. Pathol Res Pract, 1996,192(12):1195-1201.
[84]Rajagopal S, Moskal T L, Wang H, et al. Efficacy and specificity of antisense laminin cahin-specific expression vestors in blocking laminin-induction by TGFβ1: effect of laminin blockade on TGF β 1-mediated cellular responses[J]. J Cell Physiol, 1999,178(3):296-303.
[85]Vollmers HP, Imhof BA, Braun S, et al. Monoclonal antibodies which prevent experimental lung metastases:interference with adhesion of tumour cells to laminin[J]. FEBS Lett,1984,172(1):17-20.
[86]Trombetta ES, Parodi AJ. Quality control and protein folding in the secretory pathway[J]. Annu Rev Cell Dev Biol,2003,19:649-76
[87]Dong D, Dubeau L, Bading J, et al. Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors[J]. Hum Gene Ther,2004,15 (6):553-561.
[88]Misra UK, Deedwania R, Pizzo SV. Activation and crosstalk between Akt, NF-κ B, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78[J]. J Biol Chem,2006,281 (19):13694-136707.
[89]Knowlton JR, Jolnston SC, Whitby FG, et al. Structure of the proteasome activator REGalpha (PA28alpha) [J]. Nature,1997,390(6660):639-643.
[90]李洁,谢文光,沈备奋等.GAPDH功能多样性研究进展[J].军事医学科学院院刊,2006,30(5)：483—486.
[91]Merx MW, Flogel U, Stumpe T, et al. Myoglobin facilitates oxygen diffusion[J]. FASEB J,2001,15(6):1077-9.
[92]Galluzzo M, Pennacchietti S, Rosano S, et al. Prevention of hypoxia by myoglobin expression in human tumor cells promotes differentiation and inhibits metastasis[J]. J Clin Invest,2009,119(4):865-875.
[93]Nieminen M, Henttinen T, Merinen M, et al. Vimentin function in lymphocyte adhesion and transcellular migration[J]. Nat Cell Biol,2006,8 (2):156-162.
[94]Colucci-Guyon E, Portier MM, Dunia I, et al. Mice lacking vimentin develop and reproduce without an obvious phenotype[J]. Cell,1994,79(4):679-694.
[95]Eckes B, Colucci-Guyon E, Smola H, et al.Impaired wound healing in embryonic and adult mice lacking vimentin[J]. J Cell Sci,2000,113 (Pt 13):2455-2462.
[96]Brakebusch C, Fassler R, The integrin-actin connection, an eternal love affair[J]. EMBO J,2003,22 (10):2324-2333.
[97]Calderwood DA. Integrin activation[J]. J Cell Sci,2004,117 (Pt5):657-666.
[98]van der Neut R, Krimpenfort P, Calafat J,et al. Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice[J]. Nat Genet,1996,13 (3):366-369.
[99]Gonzales M, Weksler B, Tsuruta D, et al. Structure and function of a vimentin-associated matrix adhesion in endothelial cells[J]. Mol Biol Cell,2001,12 (1):85-100.
[100]Tsuruta D,Jones JC. The vimentin cytoskeleton regulates focal contact size and adhesion of endothelial cells subjected to shear stress[J]. J Cell Sci,2003,116 (Pt24): 4977-4984.
[101]Bershadsky AD, Tint IS, Svitkina TM. Association of intermediate filaments with vinculin-containing adhesion plaques of fibroblasts[J]. Cell Motil Cytoskelet, 1987,8 (3):274-283.
[102]Esue O, Carson AA, Tseng Y, et al. A direct interaction between actin and vimentin filaments mediated by the tail domain of vimentin[J]. J Biol Chem,2006, 281 (41):30393-30399.
[103]Willipinski-Stapelfeldt B, Riethdorf S, Assmann V,et al. Change in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells[J]. Clin Cancer Res,2005,11(22),8006-8014.
[104]Hu L,Lau SH, Tzang CH, et al. Association of Vimentin overexpression and hepatocellular carcinoma metastasis[J]. Oncogene,2004,23(1):298-302.
[105]Chen YR, Juan HF, Huang HC, et al. Quantitative proteomic and genomic profiling reveals metastasis-related protein expression patterns in gastric cancer cells[J]. J Proteome Res,2006,5(10):2727-2742.
[106]Alonso SR, Tracey L, Ortiz P, et al. A High-Throughput Study in Melanoma Identifies Epithel ial-Mesenchymal Transition as a Major Determinant of Metastasis[J]. Cancer Res,2007,67(7):3450-3460.
[107]Wei J, Xu G, Zhang Y, et al. Overexpression of vimentin contributes to prostate cancer invasion and metastasis via src regulation[J]. Anticancer Res,2008,28(1 A): 327-334.
[108]Wu M,Bai X, Xu G, et al. Proteome analysis of human androgen-independent prostate cancer cell lines:Variable metastatic potentials correlated with vimentin expression[J].Proteomics,2007,7(12):1973-1983.
[109]Hendrix MJ, Seftor EA, Chu YW, et al. Coexpression of vimentin and keratins by human melanoma tumor cells correlation with invasive and metastatic potential[J]. J Natl Cancer Inst,1992,84(3):165-174.
[110]Ben-Ze'ev A, Raz A. Relationship between the organization and synthesis of vimentin and the metastatic capability of B16 melanoma cells[J]. Cancer Res, 1985,45(6):2632-2641.
[1]Jenul A, Siegcl R, Ward E, el al. Cancer statistics[J]. CA Cancer J Clin,2006, 56(3):106-130.
[2]Jemal A, Devesa SS, Harlge P, et al. Recent trends in cutaneous melanoma incidence among whites in the United States[J]. J Nati Cancer Insi,2001,93(9): 678-683.
[3]Goldstein AM, Tucker MA. Etiology, epidemiology, risk factors, and public health issues of melanoma[J]. Curr Opin Oncol,1993,5(2):358-363.
[4]Ries LA. Wiiigo PA. Miller DS, et al. The annual report of the nation on the status of cancer,1973-1997, with a special section on colorectal cancer[J]. Cancer,2000, 88(10):2398-2424.
[5]Stevens NG, LiffJ M, Weiss NS. Plantiu melanoma:is the incidence of melanoma of the sole of the fool really higher in blacks than whites? [J]. Int J Cancer,1990, 45(4):691-693.
[6]Clark WH, Tucker MA, Janipel RM. Atypical melanocytie nevi of the genital type with a discussion of reciprocal parenchymal-stromal intendtions in the biology of neoplasia[J]. Hum Pathol,1998:29(1. suppl 1):S1-S24.
[7]McNutt NS, Urmacher C, Hakimian J, et al. Malignant melanoma:morphologic patterns and immunohistochemical reactivity[J]. J Cutan Pathol,1995,22(6): 502-517.
[8]Crowson AN, Magro CM, Milim MC. The Melanocytic Proliferations: A Comprehensive Textbook of Pigmental lesions[M]. New York. NY:Wiley-Liss, 2001:539.
[9]Fiotte TJ, Mibm MC. Lentigo maligna and malignant melanoma in situ, lentigo maligna type[J]. Hum Pathol,1999,30(5):533-536.
[10]Tannous ZS, Lemer LH, Duncan LM, et al. Progression to invasive melanoma from malignant melanoma in situ. Lentigo maligna type[J]. Hum Pathol,2000,31(6):705-708.
[11]Anderson WF, Pfeiffer RM, Tucker MA, et al. Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma. Cancer, 2009,115(18):4176-4185.
[12]Lachiewicz AM, Berwick M, Wiggins CL, et al. Epidemiologic support for melanoma heterogeneity using the surveillance, epidemiology, and end results program[J]. J Invest Dermatol,2008,128(5):1340-1342.
[13]Bradford PT, Goldstein AM, McMaster ML, et al. Acral lentiginous melanoma: incidence and survival patterns in theUnitedStates,1986-2005[J]. Arch Dermatol, 2009,145(4):427-434.
[14]Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma:I. Common and atypical naevi[J]. Eur J Cancer,2005, 41(1):28-44.
[15]Olsen CM, Zens MS, Stukel TA, et al. Nevus density and melanoma risk in women:a pooled analysis to test the divergent pathway hypothesis[J]. Int J Cancer, 2009,124(4):937-944.
[16]Chang YM, Newton-Bishop JA, Bishop DT, et al. A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes[J]. Int J Cancer,2009,124(2):420-428.
[17]Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma[J]. JAMA,1997,277(18):1439-1444.
[18]IARCIn:IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Solar and Ultraviolet Radiation, vol.55. Lyon (France):IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; 1992.
[19]Yu CL, Li Y, Freedman DM, et al. Assessment of lifetime cumulative sun exposure using a self-administered questionnaire:reliability of two approaches[J]. Cancer Epidemiol Biomarkers Prev,2009,18(2):464-471.
[20]Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma:Ⅱ. Sun exposure[J]. Eur J Cancer,2005,41(1):45-60.
[21]Rutter JL, Bromley CM, Goldstein AM, et al. Heterogeneity of risk for melanoma and pancreatic and digestive malignancies:a melanoma case-control study[J]. Cancer,2004,101(12):2809-16.
[22]Goldstein AM, Chan M, Harland M, et al. Features associated with germline CDKN2A mutations:a GenoMEL study of melanoma-prone families from three continents[J]. J Med Genet,2007,44(2):99-106.
[23]Goldstein AM, Chan M, Harland M, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL[J]. Cancer Res,2006,66(20):9818-9828.
[24]Goldstein AM, Landi MT, Tsang S, et al. Association of MCI R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations[J]. Cancer Epidemiol Biomarkers Prev,2005,14(9):2208-2212.
[25]Clark WH, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin[J]. Cancer RES,1969, 29(3):705-727.
[26]Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma[J]. ANN Surg,1970,172(5):902-908.
[27]Balch CM, Soong SJ, Gershenwaid JE,et al. Prognostic factors analysis of 17600 melanoma patienis:validation of the American Joint Committee on Cancer melanoma staging system[J]. J Clin Oncol,2001,19(16):3622-3634.
[28]Balch CM, Buaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer siaging system for cutaneous melanoma[J]. J Clin Oncol,2001,19(16):3635-3648.
[29]Balch CM, Btizaid AC, Soong SJ, et al. New TNM melanoma staging system:linking biology and natural history to clinical outcomes[J]. Semin Surg oncol,2003,21(1):43-52.
[30]Yan S, Brennick JB. False-positive rate of immunoperoxidase stains for MARTI/Melan A in lymph nodes[J]. Am J Surg Pathol,2004,28(5):596-600.
[31]Elder DE, Guerry D, Epstein MN, et al. Invasive malignant melanomas lacking competence for metastasis[J]. Am J Dermatopathol,1984:6(suppl):55-61.
[32]Guerry D, Synnestvedt M, Elder DE, et al. lessons from tumor progression:the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent[J]. J Invest Dermatol,1993,100(3):342S-345S.
[33]Barnhill RL, Katzen J, Spatz A, et al. The importance of Mitotic rate as a prognostic factor for localized cutaneous melanoma[J]. J Cutan Pathol,2005, 32(4):268-273.
[34]Azzola MF, Shaw HM, Thompson JF, et al. Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma:an analysis of 3661 patients from a single center[J]. Cancer,2003, 97(6):1488-1498.
[35]Gimotty PA, Guerry D,Ming ME, et al. Thin primary cutaneous malignant melanoma:a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging[J]. J Clin Oncol,2004,22(18): 3668-3676.
[36]Guitart J, Lowe L, Piepkom M, et al. Histological characteristics of metastasizing thin melanomas:a case-control study of 43 cases[J]. Arch Dermatol, 2002,138(5):603-608.
[37]Slingluff CL, Vollmer RT, Reintgen DS, et al. Lethal "thin" malignant melanoma:identifying patients at risk[J]. Ann Surg,1988,208(2):150-161.
[38]Clemente CG, Mihm MC, Bufalina R, et al. Prognoslic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma[J]. Cancer,1996,77(7):1303-1310.
[39]Elder DE, Guerry D, VanHom M, et al. The role of lymph node dissection for clinical stage malignant melanoma of intermediate thickness (1.51-3.99 mm) [J]. Cancer,1985,56(2):413-418.
[40]Mraz-Gemhard S, Sagebiel RW, Kashani-Sabet M, et al. Prediction of sentinel lymph node micro metastasis by histological features in primary cutaneous malignant melanoma[J]. Arch Dermatol,1998,134(8):983-987.
[41]Bamliill R, Dy K, Lugassy C, et al. Angiotropism in cutaneous melanoma:a prognostic factor strongly predicting risk for metastasis[J]. J Invest Dermatol,2002, 119(3):705-706.
[42]Miller AJ, Mihm MC. Melanoma[J]. N Engl J Med,2006,355(1):51-65.
[43]DeRisi J, Penland L, Brown PO, et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer[J]. Nat Genet,1996,14(4):457-460.
[44]Ryu B, Kim DS, DeLuca AM, et al. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression[J]. PLoS ONE,2007,2(7):e594.
[45]Hoek K, Rimm DL, Williams KR, et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas[J]. Cancer Res,2004, 64(15):5270-5282.
[46]Smith AP, Hoek K, Becker D. Whole-genome expression profiling of the melanoma progression pathway reveals marked molecular differences between nevi/melanoma in situ and advanced-stage melanomas[J]. Cancer Biol Ther,2005, 4(9):1018-1029.
[47]Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome[J]. J Natl Cancer Inst,2006, 98(7):472-482.
[48]Nambiar S, Mirmohammadsadegh A, Doroudi R, et al. Signaling networks in cutaneous melanoma metastasis identified by complementary DNA microarrays[J]. Arch Dermatol,2005,141 (2):165-173.
[49]Mandruzzato S, Callegaro A, Turcatel G, et al. A gene expression signature associated with survival in metastatic melanoma[J]. J Transl Med,2006, Nov 27, 4:50.
[50]Seftor EA, Brown KM, Chin L, et al. Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment[J]. Cancer Res,2005, 65(22):10164-10169.
[51]Feinberg AP. Phenotypic plasticity and the epigenetics of human disease[J]. Nature,2007,447(7143):433-440.
[52]Muthusamy V, Duraisamy S, Bradbury CM, et al. Epigenetic silencing of novel tumor suppressors in malignant melanoma[J]. Cancer Res,2006,66(23): 11187-11193.
[53]Hoon DS, Spugnardi M, Kuo C, et al. Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients[J]. Oncogene,2004,23(22):4014-4022.
[54]Furuta J, Nobeyama Y, Umebayashi Y, et al. Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas[J]. Cancer Res,2006,66(12):6080-6086.
[55]Spugnardi M, Tommasi S, Dammann R, et al. Epigenetic inactivation of RAS association domain family protein 1 (RASSF1A) in malignant cutaneous melanoma[J]. Cancer Res,2003,63(7):1639-1643.
[56]Worm J, Christensen C, Grφnbaek K, et al. Genetic and epigenetic alterations of the APC gene in malignant melanoma[J]. Oncogene,2004,23(3):5215-5226.
[57]Worm J, Bartkova J, Kirkin AF, et al. Aberrant p27Kipl promoter methylation in malignant melanoma[J]. Oncogene,2000,19(44):5111-5115.
[58]Gonzalgo ML, Bender CM, You EH, et al. Low frequency of p16/CDKN2A methylation in sporadic melanoma:comparative approaches for methylation analysis of primary tumors[J]. Cancer Res,1997,57(23):5336-5347.
[59]Muthusamy V, Duraisamy S, Bradbury CM, et al. Epigenetic silencing of novel tumor suppressors in malignant melanoma[J]. Cancer Res,2006,66(23): 11187-11193.
[60]Hellebrekers DM, Melotte V, Vire E, et al. Identification of epigenetically silenced genes in tumor endothelial cells[J]. Cancer Res,2007,67(9):4138-4148.
[61]Rothhammer T, Bosserhoff AK. Epigenetic events in malignant melanoma[J]. Pigment Cell Res,2007,20(2):92-111.
[62]Hoek K, Rimm DL, Williams KR., et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas[J]. Cancer Res,2004, 64(15):5270-5282.
[63]Bittner M, Meltzer P, Chen Y, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling[J]. Nature,2000,406 (6795):536-540.
[64]Haqq C, Nosrati M, Sudilovsky D, et al. The gene expression signatures of melanoma progression[J]. Proc Natl Acad Sci,2005,102(17):6092-6097.
[65]Seykora JT,. Elenitsas DR,. Horng WH, et al. Gene expression profiling of melanocytic lesions[J]. Am J Dermatopathol,2003,25(1):6-11.
[66]Halaban R, Miglarese MR, Smicun Y, et al. Melanomas, from cell cycle point of view[J]. Int J Mol Med,1998,1(2):419-425.
[67]Bachmann IM, Straume O, Puntervoll HE, et al. Importance of P-cadherin, beta-catenin and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma[J]. Clin Cancer Res,2005,11(24pt1):8606-8614.
[68]Satyamoorthy K, Muyrers J, Meier F, et al. Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication[J]. Oncogene,2001,20(34):4676-4684.
[69]St Croix B, Rago C, Velculescu V, et al. Genes expressed in human tumor endothelium[J]. Science,2000,289(5482):1197-1202.
[70]Gutheil JC, Campbell TN, Pierce PR et al. Targeted antiangiogenic therapy for cancer using Vitaxin:A humanized monoclonal antibody to the integrin alphavbeta3 [J]. Clin Cancer Res,2000,6(8):3056-3061.
[71]Pandey A, Mann M. Proteomics to study genes and genomes[J]. Nature,2000, 405(11):837-846.
[72]Gorg A, Weiss W, Dunn M. Current two-dimensional electrophoresis technology for proteomics[J]. Proteomics,2004,4(12):3665-3685.
[73]Cargile BJ, Sevinsky JR, Essader AS. Immobilized pH gradient isoelectric focusing as a first dimension separation in shotgun proteomics[J]. J Biomol Tech, 2005,16(3):181-189.
[74]龙晓辉,莫志宏,张耀洲.基于二维凝胶电泳的蛋白质定量分析技术[J].化学进展,2006,18(4)：474-481.
[75]Huang SK, Darfler MM, Nicholl MB,et al. LC/MS-based quantitative proteomic analysis of paraffin-embedded archival melanomas reveals potential proteomic biomarkers associated with metastasis[J]. PLoS One,2009,4(2):e4430
[76]Rondepierre F, Bouchon B, Papon J, et al. Proteomic studies of B16 lines: involvement of annexin A1 in melanoma dissemination[J]. Biochim Biophys Acta, 2009,1794(1):61-9。
[77]Al-Ghoul M, Bruck TB, Lauer-Fields JL,et al. Comparative proteomic analysis of matched primary and metastatic melanoma cell lines[J]. J Proteome Res, 2008,7(9):4107-4018.