摘要
Objective:To explore the expression of adhesion factor E-cadherin and transcriptional factor Snail in Thyroid cancer,Thyroid adenoma and its clinical significance.
Method:The SP immunohistochemisty method was used to investigate the expreesion of adhesion factor E-cadherin and transcriptional factor Snail in 20 Thyroid adenoma,46 Thyroid cancer.
Result:The positive rate of E-cadherin in Thyroid adenoma was 75%,which was far higher than that in Thyroid cancer 26.1%(p<0.05).The positive rate of Snail in Thyroid adenoma was 30%,which was far lower than that in Thyroid cancer 65.2%(p<0.05).The expression of adhesion factor E-cadherin and transcriptional factor Snail was significantly related with the lymph node metastasis and the staging of TNM (p<0.05),and unrelated with the pathologic type, the age of patient and the sex of patient (p>0.05). There was negative correlation between the expression of E-cadherin and Snail in Thyroid cancer(rs=—0.710).
Conclusions:
1 The low expression of E-cadherin and high expression of snail may be one of the important biological symbol of vicious transformation in Thyroid cancer.
2 The low expression of E-cadherin and high expression of snail may be can increase the ability of invasion and metastasis in tumour cell.
3 Snail may be induce the occurring of EMT by influencing E-cadherin in Thyroid cancer, Snail and E-cadherin are significant negative correlation.
引文
[1]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.
[2]潘漪莲,黄勇等,上皮细胞间质转化与肿瘤[J],国际肿瘤学杂志,2010,37(5):348-351.
[3]Robert L.The extracellular matrix in development and regeneration [JJ.Int J Dev Biol,2004,48(8):687-694.
[4]Kalluri R, Neilson EC.Epithelial-mesenchymal transition and its impliations for fibrosis,J ClinInvest,2003,112:1776-1784.
[5]Boyer B,Valles AM,Edme N.Induction and regulation of epithelial= mesenchymal transitions[J].Biochem pharmacol,2000,60(8):1091-1099.
[6]Christofori G,Semb H.The role of the cell-arlhesion molecule E-cadherin as a tumour-suppressor gene [J].Trends Biochem Sci,1999,24(2):73-76.
[7]李存玺,章静波。细胞与细胞粘附机制[A].高进。癌的侵袭及转移[M].北京:北京医科大学、协和医科大学联合出版社,1996.133.
[8]张阿丽,王全胜等。Snail及E-cadherin在上皮性肿瘤中的表达及其临床意义[J],肿瘤,2006,26(5):469-471.
[9]Takeichi M.Morphogenetic roles of classic cadherins[J].Curr Opin Cell Biol, 1995,7(5):619-627.
[10]陆虹旻,马俐君等,上皮间质细胞转化的分子机制及其在肿瘤转移中的作用[J],中国肿瘤生物治疗杂志,2009,16(5):541-545.
[11]Tamura G,Yin J,Wang S,et al.E-cadherin gene promoter hypermethylation in primary human gastric carcinomas.J Natl Cancer Inst,2000,92(7):569-573.
[12]Mingchao Devereux TR,Stockton P,et al.Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis.Exp Toxicol Pathol,2001,53(4):237-246.
[13]Gavallaro U,Schaffhauser B,Christofori G.Cadherins and the tumour progression:is it all in a switch[J]?Cancer lett,2002,176(2):123-128.
[14]Come C, Arnoux V, Bibeau F,et al.Roles of the transcription factors snail and slug during mammary morphogenesis and breast carcinoma progression[J].J Mammay Gland Biol Neoplasis,2004,9(2):183-193.
[15]Come C,Magnino F,Bibeau F.et al.Snail and slug play distinct roles during breast carcinoma progression.Clin Cancer Res,2006,12(18):5395-5402.
[16]刘阁玲,齐凤英等,血管内皮生长因子、基质金属蛋白酶-9和E-钙黏素在甲状腺癌组织中的表达及意义[J],中国综合临床,2005,21(5):454-456.
[17]马伟,吴继锋等,转录因子Snail及黏附分子E-cadherin在胃癌中的表达[J],临床与实验病理学杂志,2007,23(1):48-52.
[18]YAP A S,CRAMPTON M S,HARDIN J.Making and breaking contacts:the cellular biology of cadherin regulation[J].Curr Opin Cell Biol,2007, 19(5):508-514.
[19]Cowin P,Rowlands TM,Hatsell SJ.Cadherins and catenins in breast cancer [J].Curr Opin Cell Biol,2005,17(5):499-508.
[20]张莉丽,张布衣,姚根有.组织芯片检测snail mRNA的表达及其与胃癌的关系[J].浙江临床医学,2008,10(8):1014-1015.
[21]阎爱华,孙洋,王靖等.宫颈鳞癌组织中SnailmRNA和蛋白的表达[J]Journal of Zhengzhou Univercity(Medical Sciences),2008,43(6):1179-1182.
[22]郑伯安,邓高里,董全进等.表皮-钙黏附素和Snail蛋白的表达与大肠癌侵袭转移及预后的关系[J],2010,32(2):111-116.
[23]郑振波,张布衣,姚根有.通过组织芯片分析Snail、claudin-1mRNA表达与胃癌的关系[J].医学研究杂志,2006,35(12):29-32.
[24]殷涛,王春友等,胰腺癌组织中Snail与E-钙黏素蛋白的表达及临床意义[J],中华医学杂志,2006,86(40):2821-2825.
[25]Miyoshi A,Kitajirna Y,Sumi K,et al.Snail and SIPI increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells[J].Br J Cancer, 2004,90(6):1265-1273.
[26]王爽,吕丽春等,转录因子Snail及黏附分子E-cadherin在鼻咽癌中的表达[J],广东医学,201031(7):845-847.
[27]Poser I,Dominguez D.de Herreros A J.et al.Adhesion Molecule in Cancer biology[J].J Biol Chem,2001,276(27):24661.
[28]Yokoama K.Kamats N,Hayashi E,et al,Reverse correlation of E-cadherin and Snail expression in oral squamous cell carcinoma cells in vitro[J].Oral Oncol 2001,37:65-71.
[29]Blechschmidt K,Sassen S,Schmalfeldt B.et al,The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients[J],Br J Cancer,2008,98(2):489-495.
[30]Blanco MJ,Moreno-Bueno C,SarrioD,et al.Correlation of Snail expression with histological grade and lymph node status in breast carcinomas [J].Oncngene, 2002,21(20):3241-3246.
[1]Robert L.The extracellular matrix in development and regeneration [J].Int J Dev Biol,2004,48(8):687-694.
[2]Kalluri R, Neilson EC.Epithelial-mesenchymal transition and its impliations for fibrosis,J Clin Invest,2003,112:1776-1784.
[3]Boyer B,Valles AM.Edme N.Induction and regulation of epithelial= mesenchy-mal transitions[J].Biochem pharmacol,2000,60(8):1091-1099.
[4]Kalluri R.EMT:when epithelial cells decide to become mesenchymal-like cells.J Clin Invest,2009,119:1417-1419.doi:10.1172/JC139675.
[5]Takeichi M.Morphogenetic roles of classic cadherins[J].Curr Opin Cell Biol, 1995,7(5):619-627.
[6]Christofori G,Semb H.The role of the cell-arlhesion molecule E-cadherin as a tumour-suppressor gene [J].Trends Biochem Sci,1999,24(2):73-76.
[7]Cowin P.Rowlands TM,Hatsell SJ.Cadherins and catenins in breast cancer [J].Curr Opin Cell Biol,2005,17(5):499-508.
[8]YAP A S,CRAMPTON M S,HARDIN J.Making and breaking contacts:the cellular biology of cadherin regulation[J].Curr Opin Cell Biol,2007,19(5): 508-514.
[9]NATALWALA A,SPYCHAL R,TSELEPIS C.Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract[J].World J Gastroenterol,2008,14(24):3792-3797.
[10]Stoker M,Perryman M. An epithelial scatter factor released by embryo fibroblasts[J].J Cell Sci,1985,77:209-223.
[11]Menakongka A,Suthiphongchai T.Involvement of PI3K and ERK1/2 pathways in hepatocyte growths in hepatocyte growth factor-induced cholan-giocarcinoma cell invasion[J].World J Gastroenterol,2010,16(6):713-722.
[12]李余发,梁莉,丁彦青等,上皮—间质转化相关的信号传导通路[J],国际肿瘤学杂志,2009,36(2):83-85
[13]Bates RC.Colorectal cancer progression:Integrin alphavbeta6 and the epithelial-mesenchymaltransition(EMT)[J].CellCycle.2005,4(10):1350-1352.
[14]Roberts AB,Tian F,Byfield SD,et al.Smad3 is key to TGF-betamediated epithelial-to- mesenchymal transition,fibrosis, tumor suppression and metastasis.Cytokine Growth Factor Rev,2006,17(1-2):19-27.
[15]Morali OG,Delmas V, Moore R,et al.IGF-Ⅱ induces rapid (3-catenin relocation to the nucleus during epithelium to mesenchyme transition[J]. Oncogene,2001, 20(36):4942-4950.
[16]Lee MY,Chou CY,Tang MJ,et al.Epithelial-mesenchymal transition in cervical cancer:correlation with tumor progression,epidermal growth factor receptor overexpression and snail up-regulation[J].Clin Cancer Res,2008,14(15):4743-4750.
[17]Thomson SE,Buck F,Petti G,et al.Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition[J].Cancer Res,2005, 65(20):9455-9462
[18]Gonzalez-Moreno O,Lecanda J,Green JE,et al.VEGF elicits epithelial-mesenchymal transition(EMT)in prostate intraepithelial neoplasia(PIN)-like cells via an autocrine loop[J].Exp Cell Res,2010,316(4):554-567.
[19]Kim D,Cheng GZ,Lindsley CW,et al.Targeting the phosphatidylinositol-3 kinase/Akt pathway for the treatment of cancer.Curr Opin Investig Drugs,2005, 6(12):1250-1258.
[20]Grille SJ,Bellacosa A,Upson J,et al, The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines.Cancer Res,2003,63(9):2172-2178.
[21]Smallborn M,Murray MJ,Saint R,The epithelial-mesenchymal transition of the Drosophila mesoderm requires the Rho GTP exchange factor Pebble Development,2004,131 (11);2641-2651.
[22]Guarino M,Rubino B,Ballabio G.The role of epithelial-mesenchymal-transition in cancer pathology.Pathology,2007,39(3):305-318.
[23]Thomas MC,Tikellis C,Kantharidis p,et al.The role of advanced glycation in reduced organic cation transport associated with experimental diabetes.J Pharmscol Exp Ther,2004,311(2);456-466.
[24]陆虹旻,马俐君等,上皮间质细胞转化的分子机制及其在肿瘤转移中的作用[J],中国肿瘤生物治疗杂志,2009,16(5):541-545.
[25]Ansieau S,Bastid J,Dorean A,et al.Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence[J]. Cancer Cell,2008,14(1):79-89.
[26]Postigo AA.Opposing functions of ZEB proteins in the regulation of the TGFp/BMP signaling pathway[J].EMBO J,2003,22(10):2443-2452.
[27]Song Y, Washington MK,Crawford HC.Loss of FOXA1/2 is essential for the epithelial to mesenchymal transition in pancreatic cancer [J].Cancer Res,2010, 70(5):2115-2125.
[28]Min C,Eddy SF,Sherr DH,et al.NF-kappaB and epithelial to mesenchymal transition of cancer[J].J Cell Biochem,2008,104(3):733-744.
[29]Chua HL.Bhat-Nakshatri P.Clare SE,et al.NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells:potential involvement of ZEB-land ZEB-2[J].Oncogene,2007, 26(5):711-724.
[30]Fernando RI,Litzinger M,Trono P,et al.The T-box transcription factor Brach-yury promotes epithelial-mesenchymal transition in human tumor cells[J].J Clin Invest,2010 120 (2):533-544.
[31]Stover DG,Bierie B,Moses HL.A delicate halance:TGF-beta and the turnor microenvironment[J] Cell Biochem,2007,101(4):851-861.
[32]Mohla S.Tumor microenvironment[J].J Cell biochem,2007,101(4):801-804.
[33]Li H,Fan X,Houghton J.Tumor microenvironment.The role of the tumor stroma in cancer[J].J Cell Biochem,2007,101(4):805-815.
[34]Gotzmann J.Mikula M,Eger A,et al.Molecular aspects of epithelial cell plasticity:implications for local tumor invasion and metastasis [J].Mutst Res, 2004.566 (1):9-20.
[35]Mimeault M.Batra SK.Interplay of distinct growth faxtors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies[J].Ann oncol,2007,18(10):1605-1619.
[36]Savagner P.Leaving the neighborhood:molecular mechanisms involved during epithrlial-mesenchymal transition.[J].Bioeasays,2001,23(10):912-923.
[37]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.
[38]潘漪莲,黄勇等,上皮细胞间质转化与肿瘤[J],国际肿瘤学杂志,2010,37(5):348-351.
[39]王雅娟,胡洁等,Tiaml与大肠癌细胞EMT的关系[J],世界华人消化杂志,2009,17(32):3337-3341.
[40]马伟,吴继锋等,转录因子Snail及黏附分子E-cadherin在胃癌中的表达[J],临床与实验病理学杂志,2007,23(1):48-52.
[41]王爽,吕丽春等,转录因子Snail及黏附分子E-cadherin在鼻咽癌中的表达[J],广东医学,201031(7):845-847.
[42]Yang J,Mani S A.Donaher J L,et al.Twist,a master regulator of morphogenesis, plays an essential role in tumor metastasis [J],Cell,2004,117(7);927-939.
[43]殷涛,王春友等,胰腺癌组织中Snail与E-钙黏素蛋白的表达及临床意义[J],中华医学杂志,200,86(40):2821-2825.
[44]Mani SA,Guo w,Liao MJ,et al.The epithelial-mesenchymal transition generates cells with properties of stem cells.Cell,2008,133(4):704-715.
[45]Brabletz T,Jung A,Spaderna S,et al.Opinion:Migrating cancer stem cells an integrated concept of malignant tumour progression[J].Nat Rev Cancer,2005, 5(9):744-749.
[46]张可华,宋建国等,EMT与肿瘤,生命的化学[J],2008,28(5):523-526.
[47]Robson EJ,Khaled WT,Abell K,et al.Epithelial-to-mesenchymal transition confers resistance to apoptosis in three murine mammary epithelial cell lines.Differentiation,2006,74(5):254-264.
[48]冯炜红,张斌等,上皮-间质转化与乳腺癌[J],国际肿瘤学杂志,2011,38(2):121-123.
[49]唐勇,王辉等,EMT经p38-MAPK调节乳腺癌MCF-7细胞P-gp介导的多药耐药[J],中国肿瘤生物治疗杂志,2010,17(2):144-146.
[50]陈文元,魏婷等,结直肠癌LoVo细胞株EMT逆转前后耐药相关ABC转运蛋白基因的变化[J],广州医学院学报,2010,38(3):21-23.
[51]张飞,史玉荣等,乳腺癌多药耐药细胞MCF-7/ADR中Twist的表达及EMT现象的实验研究[J],中国肿瘤临床,2007,34(7):361-365.