人结肠癌SW620细胞上清作用下树突状细胞内皮样分化的研究
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摘要
研究背景:
树突状细胞(dendritic cells,DCs)是目前已知的体内抗原呈递功能最强的专职抗原呈递细胞(antigen presenting cells,APCs),是启动、调控、并维持免疫反应的中心环节。在抗肿瘤免疫中发挥着重要作用。然而,许多研究证实在肿瘤患者循环血中和肿瘤周围浸润的树突状细胞的表型及其呈递功能均下降,肿瘤细胞可以分泌多种免疫抑制因子抑制DCs的功能成熟。
肿瘤的无限制生长需要血管的供应。传统理论认为肿瘤血管形成是通过血管新生(angiogenesis)即从已存在的微血管上芽生出新的毛细血管的过程,目前研究发现也可以通过血管发生(vasculogenesis)——由内皮前体细胞分化形成新血管的过程。内皮细胞(endothelial cells,ECs)可以来源于骨髓内皮前体细胞(endothelialprogenitors,EPCs)和人外周血中CD34~+细胞群。研究证实多数肿瘤细胞都高表达血管内皮生长因子(vascular endothelial growth factor,VEGF),VEGF可以通过MAPK/ERK信号途径刺激内皮细胞的增殖和分化,从而促进肿瘤血管生成。MAPK/ERK途径是体内外多种细胞分化的重要信号通路之一。
最新研究报道,在小鼠和人卵巢癌组织中发现了一种新的白细胞亚群,同时表达DCs和内皮细胞的标志。另有学者报道在肿瘤条件培养基浸润下的单核细胞能分化发育为肿瘤相关性树突细胞(tumor-associated dendritic cells,TADCs),此类细胞能在血管生成因子如VEGF和致瘤素M的诱导下分化发育为内皮样细胞(endothelial-like cells,ELCs),并且在基质胶上可以形成网状结构。本课题组前期研究发现结肠癌SW620细胞上清能抑制未成熟DCs(immature dendritic cells,iDCs)的生长过程及相关抗原表达,并且未成熟DCs在SW620细胞上清诱导下发生内皮样分化。这些研究揭示在肿瘤相关环境下DCs在抗肿瘤免疫方面受到抑制,部分DCs还发生内皮样分化。国内外近年来关于DCs的研究多集中于如何提高DCs抗肿瘤的免疫功能等方面,而肿瘤微环境下DCs的内皮样分化发生及其机制等还有待于进一步的研究。
目的:
本实验探讨结肠癌细胞SW620分泌的可溶性细胞因子营造的微环境对人外周血单个核细胞来源的不同时期DCs发生内皮样分化的影响,以及MAPK/ERK信号途径在此过程中的激活情况。
实验方法:
1.制备结肠癌SW620细胞上清液。
2.采集健康志愿者新鲜外周血,密度梯度离心法分离人外周血单个核细胞,RPMI 1640完全培养液调整细胞浓度为3×10~6/ml,接种于24孔培养板中,每孔1 ml,移入二氧化碳孵育箱(5%/CO_2,37℃)静置3 h,去除悬浮细胞,获取贴壁生长的单核细胞,加入含rhGM-CSF(100 ng/ml)、IL-4(5 ng/ml)和10%自体血清的1640培养液,第5d加入LPS(5 ng/ml)。诱导组除加入上述培养液外,分别于第2d(未成熟DCs诱导组)、第7d(成熟DCs诱导组)分组加入SW620细胞上清液。隔天半量换液,各诱导7d。分别于第9d和14d收集诱导组细胞和对照组DCs。培养过程中观察细胞形态并计数;提取各组细胞总蛋白,Western blotting检测内皮细胞特异性标志vWF、VE-cadherin的表达情况;透射电镜观察WP小体;增殖及杀伤实验观察诱导后细胞抗原呈递功能的改变;乙酰化低密度脂蛋白摄取实验(DiL-Ac-LDL uptake assay)了解诱导后细胞是否具有内皮细胞的功能;Westernblotting检测SW620细胞上清液对未成熟DCs刺激后15、30、60 min的ERK1/2水平的影响。使用ERK1/2上游激酶MEK的阻断剂PD98059,观察MAPK/ERK通路阻断后,SW620细胞上清诱导组细胞vWf、VE-cadherin的蛋白表达情况和DiL-Ac-LDL摄取功能。
3.胰蛋白酶法配合内皮细胞培养基培养原代脐静脉内皮细胞,作为阳性对照组。
采用统计学软件包SPSS 12.0进行结果的统计分析,将所得计量数据以平均数±标准差((?)±s)表示,确定方差齐性后,进行t检验或方差分析,P＜0.05为显著性差异。
结果:
1.在SW620细胞上清液诱导下,未成熟DCs诱导组细胞生长过程及其状态明显落后于对照组DCs,细胞密度较低,并且形成类管腔样和条索样结构;其对照组DCs则表现典型树突状细胞特征,细胞形态不规则,有粗细不等的毛刺状突起,有悬浮趋势;而成熟DCs诱导组细胞与其对照组DCs无明显差异。
2.Western blotting检测结果显示:未成熟DCs经SW620细胞上清液诱导7d后,内皮细胞的特异标记vWF、VE-cadherin与对照组DCs相比,均出现明显表达且两组间的差异有统计学意义。透射电镜结果显示:经SW620细胞上清液诱导的未成熟DCs胞内出现内皮细胞的特异性结构WP小体。DCs方面功能检测:未成熟DCs诱导组细胞的抗原提呈能力下降,而内皮细胞特异的乙酰化低密度脂蛋白摄取功能增强。SW620细胞上清诱导未成熟DCs以时间依赖性方式激活MAPK/ERK信号通路。PD98059阻断后vWF、VE-cadherin的蛋白表达均明显下降,DiL-Ac-LDL摄取功能也显著下降。
结论:
1.在SW620细胞上清液诱导下,DCs的生长过程和功能受抑制,并且未成熟DCs上调内皮细胞特异性标志和功能,提示其发生内皮样分化。
2.SW620细胞上清通过MAPK/ERK信号途径诱导未成熟DCs内皮样分化。使用PD98059阻断剂后可明显阻断其内皮样分化进程。
Background:
Dendritic cells(DCs) are the best professional antigen-presenting cells(APCs) of the immune system.They play the central role in initiating,regulating and maintaining immune responses.They are important for the specific anti-tumor T-cell response.However,most studies have shown that both circulating and tumor-infiltrating DCs(TIDCs) from cancer patients appear to be phenotypically and functionally defective.The tumor tissue secretes kinds of immune factors,which can inhibit maturation of DCs.
Tumors require blood supply for expansive growth.Until recently,angiogenesis, or sprouting of endothelial cells(ECs) from existing vessels,was the only accepted mechanism of tumor vascularization.Recent studies have suggested that vasculogenesis,or recruitment of endothelial progenitors(EPCs) that differentiate into endothelial cells,might contribute to the formation of tumor neovessels.The origin of this endothelium may be either bone marrow-derived EPCs or from human peripheral blood containing CD34~+ population.Increased VEGF levels have been found in a variety tumor.Numerous studies have shown that VEGF stimulates ECs proliferation and differentiation via mitogen-activated protein kinase/extracellular signal-regulated kinase(p42/44-MAPK/ERK1/2) signaling,which can contribute to vessel formation in tumor.MAPK/ERK pathway has been shown to be one of the key signaling pathways in the differentiation of various cell types both in vivo and in vitro.
Recently,a research reported a novel leukocyte subset in mouse and human ovarian carcinomas that coexpressed endothelial and dendritic cells markers.Other studies suggest the tumor-specific culture conditions induce the differentiation of tumor-invading monocytes into tumor-associated dendritic cells(TADCs).Additional incubation of tumor-associated DCs with pro-angiogenic factors,such as vascular endothelial growth factor and oncostatin M,led to transdifferentiation into endothelial-like cells.Also,they were able to form network-like structures on matrigel.Our prior studies have shown that the supernatant of SW620 can inhibit the growth of DCs and its expression of relative antigen.In additional,in the presence of the supernatant of SW620 immature DCs have the potential to differentiate into a cell type resembling endothelial-like cells(ELCs).These study indicates DCs were inhibited in anti-tumor immunity and some DCs differentiate into endothelial-like cells in tumor microenvironment.There are many reports about the use of intratumoural DCs inoculation as a means for tumor vaccination in the world,but research on endothelialisation of DCs is still limited.The effects of this phenomenon and mechanisms also need further investigation.
Experiment aim:
To study the degree of endothelialisation in the microenvironment created by dissoluble cytokines derived from colon carcinoma cells SW620 on the differentiations of different stages dendritic cells from human peripheral blood mononuclear cell(PBMC),and observe the precise role of MAPK/ERK signaling pathway in the process of dendritic cells differentiation into endothelial-like cells in vitro.
Methods:
1.The supernatant of SW620 was prepared.
2.Precursors of DCs were separated from peripheral blood mononuclear cells (PBMC) divided from healthy volunteers' peripheral blood by Ficoll density gradient centrifuge.After 3 hours incubation,remove non-adherent cells.The left precursors were cultured at 3×10~6/ml with RPMI1640 medium containing rhGM-CSF(100ng/ml), IL-4(5ng/ml).At the fifth day of culture added LPS(5ng/ml).Inaddition,the supernatant of SW620 cells were added to DCs on the 2~(nd)(immature DCs induced group),7~(th)(mature DCs induced group) days of culture in experimental group.And half changed the medium every other day and every group is cultured to continue 7 days.The DCs(DCs cultured with normo-medium) and experimental dendritic cells cultured with supernatant of SW620 were collected at 9~(th),14~(th) for further study. Observed the appearance character of DCs with microscope during the culture process. The vWF and VE-cadherin expression on the protein level was detected by western blotting.The endothelial-specific Weibel-Palade body was observed in the cytoplasm by transmission electron microscope(TEM).Mix lymphocyte reaction(MLR) and efficiency of kill SW620 cell after loaded tumor antigen reflected the ability of DCs. Ac-LDL uptake was analyzed with a microscope.The phosphorylations of ERK1/2 was assayed by western blotting method 15,30 and 60 minutes after the treatment of supernatant of SW620.In order to elucidate whether MAPK/ERK1/2 is essential for the differentiation process,we examined the effect of PD98059,a selective inhibitor of MEK1 and 2,the upstream regulator of MAPK/ERK 1 and 2 phosphorylation,on the differentiation of iDCs to ELCs.
3.Cultured masculine groups of HUVEC with trypsase and ECM.
All data were expressed as mean value±S.D and analyzed by statistical software SPSS12.0.P＜0.05 was considered to be statistically significant.Statistical analysis was performed using one-way ANOVA.
Results:
1.The immature DCs induced group cells' growth speed was slower than the control cells',and the cell density was lower.In addition,they were able to form tube-like and cord structures after 7 days of culture in the supernatant of SW620 cell. The morphologic changes of normal control cells were coincide with the typical DCs' reported.However,there was no significant difference between mature DCs induced groups and control groups.
2.Compared with the normal control groups cells,the expression of vWF and VE-cadherin in the immature DCs induced groups were increased by the tumor-conditioned medium,and there was statistics disparation between control groups and experimental groups.The endothelial-specific Weibel-Palade body was detected in the immature induced group cells' cytoplasm by TEM.The APC function of DCs is decrease than the normal control groups.Meanwhile the experimental groups had the ability to uptake DiL-Ac-LDL,which were the features of endothelial cell.Supernatant of SW620 activated the MAPK/ERK1/2 pathway in a time—dependent manner.Incubation of iDCs with MAPK/ERK1/2 phosphorylation inhibitor PD98059,blocked the sustained SW620 supernatant induced MAPK/ERK1/2 phosphorylation.Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 also blocked the expression of vWF and VE-cadherin in these cells and their differentiation to ELCs.
Conclusion:
1.The supernatant of SW620 can inhibit the growth and function of DCs and the immature DCs induced group cells showed strong expression of classical ECs characteristics.These results suggest that in the presence of the supernatant of SW620 immature DCs have the potential to differentiate into a cell type resembling endothelial-like cells(ELCs).
2.These data suggest that the supernatant of SW620 induces immature DCs differentiation into ELCs via a MAPK/ERK1/2 signaling pathway-mediated mechanism in vitro.Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 also blocked their differentiation to ELCs.
树突状细胞(dendritic cells,DCs)是目前已知的体内抗原呈递功能最强的专职抗原呈递细胞(antigen presenting cells,APCs),是启动、调控、并维持免疫反应的中心环节。在抗肿瘤免疫中发挥着重要作用。然而,许多研究证实在肿瘤患者循环血中和肿瘤周围浸润的树突状细胞的表型及其呈递功能均下降,肿瘤细胞可以分泌多种免疫抑制因子抑制DCs的功能成熟。
肿瘤的无限制生长需要血管的供应。传统理论认为肿瘤血管形成是通过血管新生(angiogenesis)即从已存在的微血管上芽生出新的毛细血管的过程,目前研究发现也可以通过血管发生(vasculogenesis)——由内皮前体细胞分化形成新血管的过程。内皮细胞(endothelial cells,ECs)可以来源于骨髓内皮前体细胞(endothelialprogenitors,EPCs)和人外周血中CD34~+细胞群。研究证实多数肿瘤细胞都高表达血管内皮生长因子(vascular endothelial growth factor,VEGF),VEGF可以通过MAPK/ERK信号途径刺激内皮细胞的增殖和分化,从而促进肿瘤血管生成。MAPK/ERK途径是体内外多种细胞分化的重要信号通路之一。
最新研究报道,在小鼠和人卵巢癌组织中发现了一种新的白细胞亚群,同时表达DCs和内皮细胞的标志。另有学者报道在肿瘤条件培养基浸润下的单核细胞能分化发育为肿瘤相关性树突细胞(tumor-associated dendritic cells,TADCs),此类细胞能在血管生成因子如VEGF和致瘤素M的诱导下分化发育为内皮样细胞(endothelial-like cells,ELCs),并且在基质胶上可以形成网状结构。本课题组前期研究发现结肠癌SW620细胞上清能抑制未成熟DCs(immature dendritic cells,iDCs)的生长过程及相关抗原表达,并且未成熟DCs在SW620细胞上清诱导下发生内皮样分化。这些研究揭示在肿瘤相关环境下DCs在抗肿瘤免疫方面受到抑制,部分DCs还发生内皮样分化。国内外近年来关于DCs的研究多集中于如何提高DCs抗肿瘤的免疫功能等方面,而肿瘤微环境下DCs的内皮样分化发生及其机制等还有待于进一步的研究。
目的:
本实验探讨结肠癌细胞SW620分泌的可溶性细胞因子营造的微环境对人外周血单个核细胞来源的不同时期DCs发生内皮样分化的影响,以及MAPK/ERK信号途径在此过程中的激活情况。
实验方法:
1.制备结肠癌SW620细胞上清液。
2.采集健康志愿者新鲜外周血,密度梯度离心法分离人外周血单个核细胞,RPMI 1640完全培养液调整细胞浓度为3×10~6/ml,接种于24孔培养板中,每孔1 ml,移入二氧化碳孵育箱(5%/CO_2,37℃)静置3 h,去除悬浮细胞,获取贴壁生长的单核细胞,加入含rhGM-CSF(100 ng/ml)、IL-4(5 ng/ml)和10%自体血清的1640培养液,第5d加入LPS(5 ng/ml)。诱导组除加入上述培养液外,分别于第2d(未成熟DCs诱导组)、第7d(成熟DCs诱导组)分组加入SW620细胞上清液。隔天半量换液,各诱导7d。分别于第9d和14d收集诱导组细胞和对照组DCs。培养过程中观察细胞形态并计数;提取各组细胞总蛋白,Western blotting检测内皮细胞特异性标志vWF、VE-cadherin的表达情况;透射电镜观察WP小体;增殖及杀伤实验观察诱导后细胞抗原呈递功能的改变;乙酰化低密度脂蛋白摄取实验(DiL-Ac-LDL uptake assay)了解诱导后细胞是否具有内皮细胞的功能;Westernblotting检测SW620细胞上清液对未成熟DCs刺激后15、30、60 min的ERK1/2水平的影响。使用ERK1/2上游激酶MEK的阻断剂PD98059,观察MAPK/ERK通路阻断后,SW620细胞上清诱导组细胞vWf、VE-cadherin的蛋白表达情况和DiL-Ac-LDL摄取功能。
3.胰蛋白酶法配合内皮细胞培养基培养原代脐静脉内皮细胞,作为阳性对照组。
采用统计学软件包SPSS 12.0进行结果的统计分析,将所得计量数据以平均数±标准差((?)±s)表示,确定方差齐性后,进行t检验或方差分析,P＜0.05为显著性差异。
结果:
1.在SW620细胞上清液诱导下,未成熟DCs诱导组细胞生长过程及其状态明显落后于对照组DCs,细胞密度较低,并且形成类管腔样和条索样结构;其对照组DCs则表现典型树突状细胞特征,细胞形态不规则,有粗细不等的毛刺状突起,有悬浮趋势;而成熟DCs诱导组细胞与其对照组DCs无明显差异。
2.Western blotting检测结果显示:未成熟DCs经SW620细胞上清液诱导7d后,内皮细胞的特异标记vWF、VE-cadherin与对照组DCs相比,均出现明显表达且两组间的差异有统计学意义。透射电镜结果显示:经SW620细胞上清液诱导的未成熟DCs胞内出现内皮细胞的特异性结构WP小体。DCs方面功能检测:未成熟DCs诱导组细胞的抗原提呈能力下降,而内皮细胞特异的乙酰化低密度脂蛋白摄取功能增强。SW620细胞上清诱导未成熟DCs以时间依赖性方式激活MAPK/ERK信号通路。PD98059阻断后vWF、VE-cadherin的蛋白表达均明显下降,DiL-Ac-LDL摄取功能也显著下降。
结论:
1.在SW620细胞上清液诱导下,DCs的生长过程和功能受抑制,并且未成熟DCs上调内皮细胞特异性标志和功能,提示其发生内皮样分化。
2.SW620细胞上清通过MAPK/ERK信号途径诱导未成熟DCs内皮样分化。使用PD98059阻断剂后可明显阻断其内皮样分化进程。
Background:
Dendritic cells(DCs) are the best professional antigen-presenting cells(APCs) of the immune system.They play the central role in initiating,regulating and maintaining immune responses.They are important for the specific anti-tumor T-cell response.However,most studies have shown that both circulating and tumor-infiltrating DCs(TIDCs) from cancer patients appear to be phenotypically and functionally defective.The tumor tissue secretes kinds of immune factors,which can inhibit maturation of DCs.
Tumors require blood supply for expansive growth.Until recently,angiogenesis, or sprouting of endothelial cells(ECs) from existing vessels,was the only accepted mechanism of tumor vascularization.Recent studies have suggested that vasculogenesis,or recruitment of endothelial progenitors(EPCs) that differentiate into endothelial cells,might contribute to the formation of tumor neovessels.The origin of this endothelium may be either bone marrow-derived EPCs or from human peripheral blood containing CD34~+ population.Increased VEGF levels have been found in a variety tumor.Numerous studies have shown that VEGF stimulates ECs proliferation and differentiation via mitogen-activated protein kinase/extracellular signal-regulated kinase(p42/44-MAPK/ERK1/2) signaling,which can contribute to vessel formation in tumor.MAPK/ERK pathway has been shown to be one of the key signaling pathways in the differentiation of various cell types both in vivo and in vitro.
Recently,a research reported a novel leukocyte subset in mouse and human ovarian carcinomas that coexpressed endothelial and dendritic cells markers.Other studies suggest the tumor-specific culture conditions induce the differentiation of tumor-invading monocytes into tumor-associated dendritic cells(TADCs).Additional incubation of tumor-associated DCs with pro-angiogenic factors,such as vascular endothelial growth factor and oncostatin M,led to transdifferentiation into endothelial-like cells.Also,they were able to form network-like structures on matrigel.Our prior studies have shown that the supernatant of SW620 can inhibit the growth of DCs and its expression of relative antigen.In additional,in the presence of the supernatant of SW620 immature DCs have the potential to differentiate into a cell type resembling endothelial-like cells(ELCs).These study indicates DCs were inhibited in anti-tumor immunity and some DCs differentiate into endothelial-like cells in tumor microenvironment.There are many reports about the use of intratumoural DCs inoculation as a means for tumor vaccination in the world,but research on endothelialisation of DCs is still limited.The effects of this phenomenon and mechanisms also need further investigation.
Experiment aim:
To study the degree of endothelialisation in the microenvironment created by dissoluble cytokines derived from colon carcinoma cells SW620 on the differentiations of different stages dendritic cells from human peripheral blood mononuclear cell(PBMC),and observe the precise role of MAPK/ERK signaling pathway in the process of dendritic cells differentiation into endothelial-like cells in vitro.
Methods:
1.The supernatant of SW620 was prepared.
2.Precursors of DCs were separated from peripheral blood mononuclear cells (PBMC) divided from healthy volunteers' peripheral blood by Ficoll density gradient centrifuge.After 3 hours incubation,remove non-adherent cells.The left precursors were cultured at 3×10~6/ml with RPMI1640 medium containing rhGM-CSF(100ng/ml), IL-4(5ng/ml).At the fifth day of culture added LPS(5ng/ml).Inaddition,the supernatant of SW620 cells were added to DCs on the 2~(nd)(immature DCs induced group),7~(th)(mature DCs induced group) days of culture in experimental group.And half changed the medium every other day and every group is cultured to continue 7 days.The DCs(DCs cultured with normo-medium) and experimental dendritic cells cultured with supernatant of SW620 were collected at 9~(th),14~(th) for further study. Observed the appearance character of DCs with microscope during the culture process. The vWF and VE-cadherin expression on the protein level was detected by western blotting.The endothelial-specific Weibel-Palade body was observed in the cytoplasm by transmission electron microscope(TEM).Mix lymphocyte reaction(MLR) and efficiency of kill SW620 cell after loaded tumor antigen reflected the ability of DCs. Ac-LDL uptake was analyzed with a microscope.The phosphorylations of ERK1/2 was assayed by western blotting method 15,30 and 60 minutes after the treatment of supernatant of SW620.In order to elucidate whether MAPK/ERK1/2 is essential for the differentiation process,we examined the effect of PD98059,a selective inhibitor of MEK1 and 2,the upstream regulator of MAPK/ERK 1 and 2 phosphorylation,on the differentiation of iDCs to ELCs.
3.Cultured masculine groups of HUVEC with trypsase and ECM.
All data were expressed as mean value±S.D and analyzed by statistical software SPSS12.0.P＜0.05 was considered to be statistically significant.Statistical analysis was performed using one-way ANOVA.
Results:
1.The immature DCs induced group cells' growth speed was slower than the control cells',and the cell density was lower.In addition,they were able to form tube-like and cord structures after 7 days of culture in the supernatant of SW620 cell. The morphologic changes of normal control cells were coincide with the typical DCs' reported.However,there was no significant difference between mature DCs induced groups and control groups.
2.Compared with the normal control groups cells,the expression of vWF and VE-cadherin in the immature DCs induced groups were increased by the tumor-conditioned medium,and there was statistics disparation between control groups and experimental groups.The endothelial-specific Weibel-Palade body was detected in the immature induced group cells' cytoplasm by TEM.The APC function of DCs is decrease than the normal control groups.Meanwhile the experimental groups had the ability to uptake DiL-Ac-LDL,which were the features of endothelial cell.Supernatant of SW620 activated the MAPK/ERK1/2 pathway in a time—dependent manner.Incubation of iDCs with MAPK/ERK1/2 phosphorylation inhibitor PD98059,blocked the sustained SW620 supernatant induced MAPK/ERK1/2 phosphorylation.Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 also blocked the expression of vWF and VE-cadherin in these cells and their differentiation to ELCs.
Conclusion:
1.The supernatant of SW620 can inhibit the growth and function of DCs and the immature DCs induced group cells showed strong expression of classical ECs characteristics.These results suggest that in the presence of the supernatant of SW620 immature DCs have the potential to differentiate into a cell type resembling endothelial-like cells(ELCs).
2.These data suggest that the supernatant of SW620 induces immature DCs differentiation into ELCs via a MAPK/ERK1/2 signaling pathway-mediated mechanism in vitro.Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 also blocked their differentiation to ELCs.
引文
[1]Gatti E,Pierre P.Understanding the cell biology of antigen presentation:the dendritic cell contribution.Curr Opin Cell Biol,2003,15(4):468-473.
[2]Bottomly,K.T cells and dendritic cells get intimate.Science,1999,283(5405):1124-1125
[3]Moingeon P.Cancer vaccines.Vaccine,2001,19(11-12):1305-1326
[4]Smyth M J,Godfrey DI,Trapani JA.A fresh look at tumor immunosurveillance and immunotherapy[J].Nat lmmunol.2002,2(4):293-299
[5]彭新青,谢蜀生.肿瘤微环境的改善与肿瘤生物治疗国外医学肿瘤学分册1998,25(2):84-87
[6]Chaux P,Favre N,Martin M,et al.Tumor-infiltrating dendritic cells are defective in their antigen presenting function and inducible B7 expression in rats.IntJ Cancer,1997,72(4):619
[7]Augustin HG.Antiangiogenic tumor therapy:will it work? Trends Pharmacol Sci.1998,19(6):216-222
[8]Bont E S,Guikema J E,Scherpen F,et al.Mobilized human CD34~+hematopoietic stem cell enhance tumor growth in a nonobese diabetic/severe combined immunodeficient mouse model of human non-Hodgkin's lymphoma [J].Cancer Res,2001.61(20):7654-7659
[9]Zachary I.VEGF signalling:integration and multi-tasking in endothelial cell biology.Biochem Soc Trans.2003;31:1171-7
[10]Cano E,Mahadevan LC.Parallel signal processing among mammalian MAPKs.Trends Biochem Sci.1995,20(3):117-22
[11]Alessi DR,Cuenda A,Cohen P,et al.PD098059 is a specific inhibitor of the activation of mitogenactivated protein kinase kinase in vitro and in vivo[J].J Biol Chem,1995,270(46):27489-27494
[12]Chen C,Farooqui M,Gupta K.Morphine stimulates vascular endothelial growth factor-like signaling in mouse retinal endothelial cells.Curr Neurovasc Res. 2006,3:171-80.
[13] Meadows KN, Bryant P, Pumiglia K. Vascular endothelial growth factor induction of the angiogenic phenotype requires Ras activation. J Biol Chem. 2001,276:49289-98.
[14] Gupta K, Kshirsagar S, Li W, Gui L, Ramakrishnan S, Gupta P, Law PY,Hebbel RP.VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res.1999; 247: 495-504.
[15] Conejo-Garcia JR, Benencia F, Courreges MC, et al. Tumor-infiltrating dendrtic cell precursors recruited by a p-defensin contribute to vasculogenesis under the influence of Vegf-A. Nature Med, 2004,10(9):950-958.
[16] Young MR, Cigal M. Tumor skewing of CD34~+ cell differentiation from a dendritic cell pathway into endothelial cells. Cancer Immunol Immunother, 2006, 55(5):558-568.
[17] Yamamoto H, Oda Y, Yao T, et al. Malignant perivascular epithelioid cell tumor of the colon: report of a case with molecular analysis. Pathol Int, 2006, 56(1): 46-50.
[18] Sihn DK, Choi HS, Chang YS, et al. Granular cell tumor of colon: report of a case and review of literature. World J Gastroenterol, 2004,10(16):2452-2454.
[19] Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature, 1998, 392(6673):245-252.
[20] Allavena P, Longoni D, etal. IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages [J].Eur J Immunol, 1998,28(1):359-369.
[21] Oyama T, Ran S, Ishida T, et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor- κB activation in hemopoittic progenitor cells[J].J Immunol, 1998,160(3): 1224-1232.
[22] Mimura K,Kono K,Takahashi A,et al .Vascular endothelial growth factor inhibits the function of human mature dendritic cels mediated by VEGF receptor-2[J]. Cancer Immunol lmmunother,2007,56(6):761-770.
[23]Lotze MT,Thomson AW.Dendritic cells:Biology and Clinical Applications[M].New York:Academic Press,1999,544.
[24]李用国,罗云萍,梁增伟等.人外周血树突状细胞的体外培养扩增.重庆医科大学学报,2001,26(1):1-3.
[25]Denis CV.Molecular cells and the biology of von Willerbrand factor.Int J Hematol,2002,75(1):3-8.
[26]Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endothelial cells for angiogenesis.Science,1997,275:964-967.
[27]吴岩、祝彼得.内皮细胞与造血调控的研究国外医学输血及血液学分册,2001,24:9-13.
[28]Choi K,et al.A common precursor for hematopoietic and endothelial cells.Development 1998,125,725-732
[29]Sozzani S,Rusnati M,Riboldi E,et al.Dendritic cell-endothelial cell cross-talk in angiogenesis.Trends Immunol.2007,28(9):385-92.
[30]Beatriz Femandez Pujl,Frances C Lucibello,et al.Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells.European Journol of Cell Biology,2001,80(1):99-110
[31]O'Neill DW,Adams S,Bhardwaj N,et al.Manipulating dendritic cell biology for the active immunotherapy of cancer.Blood,2004,104(8):2235-2236.
[32]Coventry BJ,Austyn JM,Chryssidis S,et al.Identification and isolation of CD1a positive putative tumourinfitrating dendritic cells in human breast cancer.Adv Exp Med Biol,1997,417(1):571-577.
[33]吴宏、王亚平.内皮细胞与血发生的关系国外医学输血及血液学分册,2001,24:396-399.
[34]Mufluoglu TM,Koksal N,Ozkutlu D.Evaluation of phagocytic function of macrophages in rats after partial splenectomy.J AM Coll Surg,2000,191(6):668-671.
[35]Miranda MB,McGuire TF,Johnson DE.Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of myeloid cell lines.Leukemia.2002;16:683-92.
[36]Xu S,Khoo S,Dang A,et al.Differential regulation of mitogenactivated protein/ERK kinase(MEK)1 and MEK2 and activation by a Ras-independent mechanism.Mol Endocfinol.1997,11:1618-1625.
[37]Lawrence E B,Xiang Qi,Jobn S P.Role for Extracellular Signal-Responsive Kinase-1 and -2 in Retinal Angiogenesis.IOVS,2003,44(4):1722-1731
[38]Fernandez Pujol B,Lucibello FC,Zuzarte M,Lutjens P,Muller R,Havemann K.Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells.Eur J Cell Biol.2001,80:99-110
[39]Gabrilovich DI,Chen HI,Girgis KR,et al.Production of Vascular endothelial growth factor by hunmn tumors inhibits the functional maturation of dendritic cells[J].Nat Med,1996,2(10):1096-1103.
[1]Choi,K.et al.A common precursor for hematopoietic and endothelial cells.Development,1998,125:725-732
[2]Schuch G;Heymach JV,Nomi M,et al.Endostatin inhibitsthe vascular endothelial growth factor-induced mobilization of endothelial progenitor cells.Cancer Res,2003,63(23):8345-8350.
[3]Shirakawa K,Furuhata S,Watanabe I,et al.Induction of vasculogenesis in breast cancer models.Br Jcancer,2002,87(12):1454--1461.
[4]Conejo-Garcia JR,Benencia F,Courreges MC,et al.Tumor-infiltrating dendrtic cell precursors recruited by a f3-defensin contribute to vasculogenesis under the influence of Vegf-A.Nature Med,2004,10(9):950-958.
[5]Coukos G;Benencia F,Buckanovich KJ,et al.The role of dendritic cell precursors in tumour vasculogenesis.Br J Cancer,2005,92(7):1182-1187.
[6]Conejo-Garcia JR,Coukos G,et al.Vascular leukocytes contribute to tumor vascularization.Blood,2005,105(2):679-681.
[7]Gottfried E,Kreuta M,Eissner G,et al.Differentiation of human tumour-associated dendritic cells into endothelial-like cells:an alternative pathway oftumour angiogenesis.Scand J Immunal,2007,65(4):329-335.
[8]Gatti E,Pierre P.Understanding the cell biology of antigen presentation:the dendritic cell contribution.Curr Opin Cell Biol,2003,15(4):468-473.
[9]Bottomly,K.T cells and dendritic cells get intimate.Science,1999,283(5405):1124-1125.
[10]Rissoan MC,Soumelis V,Kadowaki N,et al.Reciprocal control ofT helper cell and dendritic cell differentiation.Science,| 999,283(5405):1183-1186.
[11]Banchereau J,Steinman RM.Dendritic cells and the control of immunity.Nature,1998,392(6673):245-252.
[12]Pardoll DM.Cancer vaccines.Nature Med,1998,4(5):525-531.
[13]Shortman K,Liu Y J.Mouse and human dendritic cell subtypes.Nat.Rev. Immunol. 2002,2:151-161
[14] Colonna M, et al. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 2004, 5:1219-1226
[15] Sozzani, S. Dendritic cell trafficking: more than just Chemokines. Cytokine Growth Factor Rev. 2005,16: 581-592
[16] Pardoll D M.Cancer vaccines. Nature Med, 1998, 4(5):525-531.
[17] Strieter R M, et al.Cancer CXC chemokine networks and tumour angiogenesis. Eur. J. Cancer, 2006,42: 768-778.
[18] Banchereau J. et al.Immunobiology of dendritic cells. Annu.Rev. Immunol. 2000,18:767-811
[19] Steinman R M.Some interfaces of dendritic cell biology. APMIS, 2003, 111: 675-697
[20] Sozzani, S.Dendritic cell trafficking: more than just Chemokines. Cytokine Growth Factor Rev. 2005,16:581-592
[21] Goerdt S, Orfanos C E.Other functions, other genes: alternative activation of antigen-presenting cells.Immunity 1999,10:137-142
[22] Mantovani A, et al. Infiltration of tumours by macrophages and dendritic cells: tumour-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Novartis Found Symp. 2004,256:137-145, discussion 146-148, 259-269
[23] Riboldi E, et al.Cutting edge: proangiogenic properties of alternatively activated dendritic cells. J. Immunol. 2005,175:2788-2792
[24] Fiallo P, et al.Overexpression of vascular endothelial growth factor and its endothelial cell receptor KDR in type 1 leprosy reaction. Am. J. Trop. Med. Hyg. 2002,66:180-185
[25] Zhang M, et al.Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat. Immunol. 2004,5: 1124-1133
[26] Caux C, et al.Activation of human dendritic cells through CD40 cross-linking. J. Exp. Med. 1994,180:1263-1272
[27] Verhasselt V, et al. Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. J. Immunol. 1997,158: 2919-2925
[28] Graaf J H, et al.The presence of cytokines in Langerhans' cell histiocytosis. J. Pathol. 1996,180:400-406
[29] Konno S, et al. Interleukin-10 and Th2 cytokines differentially regulate osteopontin expression in human monocytes and dendritic cells. J. Interferon Cytokine Res. 2006,26:562-567
[30] Naldini A, et al.Cutting edge: IL-1b mediates the proangiogenic activity of osteopontin-activated human monocytes. J. Immunol. 2006,177:4267-4270
[31] Means T K, et al.The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells. J. Immunol. 2003,170:5165-5175
[32] Vermi W, et al. Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma. Blood 2006,107: 454-462
[33] Scimone M L, et al.Migration of polymorphonuclear leucocytes is influenced by dendritic cells. Immunology 2005,114:375-385
[34] Trinchieri G.Interleukin-12 and the regulation of innateresistance and adaptive immunity. Nat. Rev. Immunol. 2003,3:133-146
[35] Kanegane C, Sgadari C,Kanegane H et al.Contribution of the CXC Chemokines IP-10 and MIG to the antitumor effects of IL-12 [J]. J Leukoc Biol, 1998, 64(3): 384-392.
[36] Duda DG, Sunamura M, Lozonschi L et al. Direct in vitro evidence and in vivo analysis of the antiangiogenesis effects of interleukin-12 [J].Cancer Res, 2000, 60(4):1111-1116.
[37] Doyen V, et al.Thrombospondin 1 is an autocrine negative regulator of human dendritic cell activation. J.Exp.Med. 2003,198: 1277-1283
[38] Rusnati M, Presta M.Extracellular angiogenic growth factor interactions: an angiogenesis interactome survey. Endothelium 2006,13:93-111
[39] Garlanda C, et al.Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu. Rev. Immunol. 2005,23:337-366
[40] Doni A, et al.Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-g. J. Leukoc. Biol. 2006, 79:797-802
[41] Doni A, et al .Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendriticcells. Eur.J.Immunol. 2003, 33: 2886-2893
[42] Folkman J. What is the evidence that tumors are angiogenesis dependent ?J Natl Cancer Inat,;1990;82:4
[43] Neufeld G, Cohen T, Gengrinovitch S,et al. Vascular endothelial growth factor(VEGF) and its receptors .FASEB J,1999,(1):9-22
[44] Kiselyov A, Balakin K V, Tkachenko S E. VEGF / VEGFR signaling as a target for inhibiting angiogenesis[J].Expert Opin lnvestig Drugs, 2007,16(1):83-107
[45] Paley P J, Staskus K A, Gebhard K, et al. Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer. 1997, 80:98-106
[46] Gabrilovich D, Ishida T, Oyama T, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998 92: 4150-4166
[47] Gabrilovich D I,Chen H L,Girgis K R,et al .Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells[J].Nat Med,1996,2(10): 1096-1103.
[48] Peichev M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000,95:952-958
[49] Mimura K,et al .Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol. Immunother. 2007,56:761-770
[50] Chen L, et al. Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat. Med. 2004,10: 813-815
[51] Oyama T, Ran S, Ishida T, et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-KB activation in hemopoittic progenitor cells[J].J Immunol, 1998,160(3): 1224-1232.
[52] Mimura K, Kono K, Takahashi A,et al.Vascular endothelial growth factor inhibits the function of human mature dendritic cels mediated by VEGF receptor-2[J].Cancer lmmunol lmmunother,2007,56 (6):761—770
[53] Augustin H G. Antiangiogenic tumor therapy: will it work? Trends Pharmacol Sci. 1998,19(6):216-222
[54] Bont E S, Guikema J E, Scherpen F, et al. Mobilized human CD34~+ hematopoietic stem cell enhance tumor growth in a nonobese diabetic/severe combined immunodeficient mouse model of human non-Hodgkin's lymphoma [J]. Cancer Res,2001.61(20):7654-7659
[55] Wang L, Li L, Shojaei F, et al. Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties. Immunity,2004,21:31-41
[56] Schmeisser A, Garlichs C D, Zhang H,et al.Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions. Cardiovasc Res,2001,49:671-680
[57] Asahara T, Murohara T, Sullivan A, et al.Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997,275: 964-967
[58] Coukos G, Conejo-Garcia J R, Buckanovich R, et al. Vascular leukocytes: a population with angiogenic and immunosuppressive properties highly represented in ovarian cancer. Adv Exp Med Biol, 2007, 590:185-193.
[59] Fernandez Pujol B, Lucibello F C, Zuzarte M, et al .Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells. Eur J Cell Biol ,2001,80: 99-110
[60] Sozzani S, Rusnati M, Riboldi E, et al. Dendritic cell-endothelial cell cross-talk in angiogenesis. Trends Immunol. 2007,28(9):385-92
[2]Bottomly,K.T cells and dendritic cells get intimate.Science,1999,283(5405):1124-1125
[3]Moingeon P.Cancer vaccines.Vaccine,2001,19(11-12):1305-1326
[4]Smyth M J,Godfrey DI,Trapani JA.A fresh look at tumor immunosurveillance and immunotherapy[J].Nat lmmunol.2002,2(4):293-299
[5]彭新青,谢蜀生.肿瘤微环境的改善与肿瘤生物治疗国外医学肿瘤学分册1998,25(2):84-87
[6]Chaux P,Favre N,Martin M,et al.Tumor-infiltrating dendritic cells are defective in their antigen presenting function and inducible B7 expression in rats.IntJ Cancer,1997,72(4):619
[7]Augustin HG.Antiangiogenic tumor therapy:will it work? Trends Pharmacol Sci.1998,19(6):216-222
[8]Bont E S,Guikema J E,Scherpen F,et al.Mobilized human CD34~+hematopoietic stem cell enhance tumor growth in a nonobese diabetic/severe combined immunodeficient mouse model of human non-Hodgkin's lymphoma [J].Cancer Res,2001.61(20):7654-7659
[9]Zachary I.VEGF signalling:integration and multi-tasking in endothelial cell biology.Biochem Soc Trans.2003;31:1171-7
[10]Cano E,Mahadevan LC.Parallel signal processing among mammalian MAPKs.Trends Biochem Sci.1995,20(3):117-22
[11]Alessi DR,Cuenda A,Cohen P,et al.PD098059 is a specific inhibitor of the activation of mitogenactivated protein kinase kinase in vitro and in vivo[J].J Biol Chem,1995,270(46):27489-27494
[12]Chen C,Farooqui M,Gupta K.Morphine stimulates vascular endothelial growth factor-like signaling in mouse retinal endothelial cells.Curr Neurovasc Res. 2006,3:171-80.
[13] Meadows KN, Bryant P, Pumiglia K. Vascular endothelial growth factor induction of the angiogenic phenotype requires Ras activation. J Biol Chem. 2001,276:49289-98.
[14] Gupta K, Kshirsagar S, Li W, Gui L, Ramakrishnan S, Gupta P, Law PY,Hebbel RP.VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res.1999; 247: 495-504.
[15] Conejo-Garcia JR, Benencia F, Courreges MC, et al. Tumor-infiltrating dendrtic cell precursors recruited by a p-defensin contribute to vasculogenesis under the influence of Vegf-A. Nature Med, 2004,10(9):950-958.
[16] Young MR, Cigal M. Tumor skewing of CD34~+ cell differentiation from a dendritic cell pathway into endothelial cells. Cancer Immunol Immunother, 2006, 55(5):558-568.
[17] Yamamoto H, Oda Y, Yao T, et al. Malignant perivascular epithelioid cell tumor of the colon: report of a case with molecular analysis. Pathol Int, 2006, 56(1): 46-50.
[18] Sihn DK, Choi HS, Chang YS, et al. Granular cell tumor of colon: report of a case and review of literature. World J Gastroenterol, 2004,10(16):2452-2454.
[19] Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature, 1998, 392(6673):245-252.
[20] Allavena P, Longoni D, etal. IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages [J].Eur J Immunol, 1998,28(1):359-369.
[21] Oyama T, Ran S, Ishida T, et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor- κB activation in hemopoittic progenitor cells[J].J Immunol, 1998,160(3): 1224-1232.
[22] Mimura K,Kono K,Takahashi A,et al .Vascular endothelial growth factor inhibits the function of human mature dendritic cels mediated by VEGF receptor-2[J]. Cancer Immunol lmmunother,2007,56(6):761-770.
[23]Lotze MT,Thomson AW.Dendritic cells:Biology and Clinical Applications[M].New York:Academic Press,1999,544.
[24]李用国,罗云萍,梁增伟等.人外周血树突状细胞的体外培养扩增.重庆医科大学学报,2001,26(1):1-3.
[25]Denis CV.Molecular cells and the biology of von Willerbrand factor.Int J Hematol,2002,75(1):3-8.
[26]Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endothelial cells for angiogenesis.Science,1997,275:964-967.
[27]吴岩、祝彼得.内皮细胞与造血调控的研究国外医学输血及血液学分册,2001,24:9-13.
[28]Choi K,et al.A common precursor for hematopoietic and endothelial cells.Development 1998,125,725-732
[29]Sozzani S,Rusnati M,Riboldi E,et al.Dendritic cell-endothelial cell cross-talk in angiogenesis.Trends Immunol.2007,28(9):385-92.
[30]Beatriz Femandez Pujl,Frances C Lucibello,et al.Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells.European Journol of Cell Biology,2001,80(1):99-110
[31]O'Neill DW,Adams S,Bhardwaj N,et al.Manipulating dendritic cell biology for the active immunotherapy of cancer.Blood,2004,104(8):2235-2236.
[32]Coventry BJ,Austyn JM,Chryssidis S,et al.Identification and isolation of CD1a positive putative tumourinfitrating dendritic cells in human breast cancer.Adv Exp Med Biol,1997,417(1):571-577.
[33]吴宏、王亚平.内皮细胞与血发生的关系国外医学输血及血液学分册,2001,24:396-399.
[34]Mufluoglu TM,Koksal N,Ozkutlu D.Evaluation of phagocytic function of macrophages in rats after partial splenectomy.J AM Coll Surg,2000,191(6):668-671.
[35]Miranda MB,McGuire TF,Johnson DE.Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of myeloid cell lines.Leukemia.2002;16:683-92.
[36]Xu S,Khoo S,Dang A,et al.Differential regulation of mitogenactivated protein/ERK kinase(MEK)1 and MEK2 and activation by a Ras-independent mechanism.Mol Endocfinol.1997,11:1618-1625.
[37]Lawrence E B,Xiang Qi,Jobn S P.Role for Extracellular Signal-Responsive Kinase-1 and -2 in Retinal Angiogenesis.IOVS,2003,44(4):1722-1731
[38]Fernandez Pujol B,Lucibello FC,Zuzarte M,Lutjens P,Muller R,Havemann K.Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells.Eur J Cell Biol.2001,80:99-110
[39]Gabrilovich DI,Chen HI,Girgis KR,et al.Production of Vascular endothelial growth factor by hunmn tumors inhibits the functional maturation of dendritic cells[J].Nat Med,1996,2(10):1096-1103.
[1]Choi,K.et al.A common precursor for hematopoietic and endothelial cells.Development,1998,125:725-732
[2]Schuch G;Heymach JV,Nomi M,et al.Endostatin inhibitsthe vascular endothelial growth factor-induced mobilization of endothelial progenitor cells.Cancer Res,2003,63(23):8345-8350.
[3]Shirakawa K,Furuhata S,Watanabe I,et al.Induction of vasculogenesis in breast cancer models.Br Jcancer,2002,87(12):1454--1461.
[4]Conejo-Garcia JR,Benencia F,Courreges MC,et al.Tumor-infiltrating dendrtic cell precursors recruited by a f3-defensin contribute to vasculogenesis under the influence of Vegf-A.Nature Med,2004,10(9):950-958.
[5]Coukos G;Benencia F,Buckanovich KJ,et al.The role of dendritic cell precursors in tumour vasculogenesis.Br J Cancer,2005,92(7):1182-1187.
[6]Conejo-Garcia JR,Coukos G,et al.Vascular leukocytes contribute to tumor vascularization.Blood,2005,105(2):679-681.
[7]Gottfried E,Kreuta M,Eissner G,et al.Differentiation of human tumour-associated dendritic cells into endothelial-like cells:an alternative pathway oftumour angiogenesis.Scand J Immunal,2007,65(4):329-335.
[8]Gatti E,Pierre P.Understanding the cell biology of antigen presentation:the dendritic cell contribution.Curr Opin Cell Biol,2003,15(4):468-473.
[9]Bottomly,K.T cells and dendritic cells get intimate.Science,1999,283(5405):1124-1125.
[10]Rissoan MC,Soumelis V,Kadowaki N,et al.Reciprocal control ofT helper cell and dendritic cell differentiation.Science,| 999,283(5405):1183-1186.
[11]Banchereau J,Steinman RM.Dendritic cells and the control of immunity.Nature,1998,392(6673):245-252.
[12]Pardoll DM.Cancer vaccines.Nature Med,1998,4(5):525-531.
[13]Shortman K,Liu Y J.Mouse and human dendritic cell subtypes.Nat.Rev. Immunol. 2002,2:151-161
[14] Colonna M, et al. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 2004, 5:1219-1226
[15] Sozzani, S. Dendritic cell trafficking: more than just Chemokines. Cytokine Growth Factor Rev. 2005,16: 581-592
[16] Pardoll D M.Cancer vaccines. Nature Med, 1998, 4(5):525-531.
[17] Strieter R M, et al.Cancer CXC chemokine networks and tumour angiogenesis. Eur. J. Cancer, 2006,42: 768-778.
[18] Banchereau J. et al.Immunobiology of dendritic cells. Annu.Rev. Immunol. 2000,18:767-811
[19] Steinman R M.Some interfaces of dendritic cell biology. APMIS, 2003, 111: 675-697
[20] Sozzani, S.Dendritic cell trafficking: more than just Chemokines. Cytokine Growth Factor Rev. 2005,16:581-592
[21] Goerdt S, Orfanos C E.Other functions, other genes: alternative activation of antigen-presenting cells.Immunity 1999,10:137-142
[22] Mantovani A, et al. Infiltration of tumours by macrophages and dendritic cells: tumour-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Novartis Found Symp. 2004,256:137-145, discussion 146-148, 259-269
[23] Riboldi E, et al.Cutting edge: proangiogenic properties of alternatively activated dendritic cells. J. Immunol. 2005,175:2788-2792
[24] Fiallo P, et al.Overexpression of vascular endothelial growth factor and its endothelial cell receptor KDR in type 1 leprosy reaction. Am. J. Trop. Med. Hyg. 2002,66:180-185
[25] Zhang M, et al.Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat. Immunol. 2004,5: 1124-1133
[26] Caux C, et al.Activation of human dendritic cells through CD40 cross-linking. J. Exp. Med. 1994,180:1263-1272
[27] Verhasselt V, et al. Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. J. Immunol. 1997,158: 2919-2925
[28] Graaf J H, et al.The presence of cytokines in Langerhans' cell histiocytosis. J. Pathol. 1996,180:400-406
[29] Konno S, et al. Interleukin-10 and Th2 cytokines differentially regulate osteopontin expression in human monocytes and dendritic cells. J. Interferon Cytokine Res. 2006,26:562-567
[30] Naldini A, et al.Cutting edge: IL-1b mediates the proangiogenic activity of osteopontin-activated human monocytes. J. Immunol. 2006,177:4267-4270
[31] Means T K, et al.The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells. J. Immunol. 2003,170:5165-5175
[32] Vermi W, et al. Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma. Blood 2006,107: 454-462
[33] Scimone M L, et al.Migration of polymorphonuclear leucocytes is influenced by dendritic cells. Immunology 2005,114:375-385
[34] Trinchieri G.Interleukin-12 and the regulation of innateresistance and adaptive immunity. Nat. Rev. Immunol. 2003,3:133-146
[35] Kanegane C, Sgadari C,Kanegane H et al.Contribution of the CXC Chemokines IP-10 and MIG to the antitumor effects of IL-12 [J]. J Leukoc Biol, 1998, 64(3): 384-392.
[36] Duda DG, Sunamura M, Lozonschi L et al. Direct in vitro evidence and in vivo analysis of the antiangiogenesis effects of interleukin-12 [J].Cancer Res, 2000, 60(4):1111-1116.
[37] Doyen V, et al.Thrombospondin 1 is an autocrine negative regulator of human dendritic cell activation. J.Exp.Med. 2003,198: 1277-1283
[38] Rusnati M, Presta M.Extracellular angiogenic growth factor interactions: an angiogenesis interactome survey. Endothelium 2006,13:93-111
[39] Garlanda C, et al.Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu. Rev. Immunol. 2005,23:337-366
[40] Doni A, et al.Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-g. J. Leukoc. Biol. 2006, 79:797-802
[41] Doni A, et al .Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendriticcells. Eur.J.Immunol. 2003, 33: 2886-2893
[42] Folkman J. What is the evidence that tumors are angiogenesis dependent ?J Natl Cancer Inat,;1990;82:4
[43] Neufeld G, Cohen T, Gengrinovitch S,et al. Vascular endothelial growth factor(VEGF) and its receptors .FASEB J,1999,(1):9-22
[44] Kiselyov A, Balakin K V, Tkachenko S E. VEGF / VEGFR signaling as a target for inhibiting angiogenesis[J].Expert Opin lnvestig Drugs, 2007,16(1):83-107
[45] Paley P J, Staskus K A, Gebhard K, et al. Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer. 1997, 80:98-106
[46] Gabrilovich D, Ishida T, Oyama T, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998 92: 4150-4166
[47] Gabrilovich D I,Chen H L,Girgis K R,et al .Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells[J].Nat Med,1996,2(10): 1096-1103.
[48] Peichev M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000,95:952-958
[49] Mimura K,et al .Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol. Immunother. 2007,56:761-770
[50] Chen L, et al. Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat. Med. 2004,10: 813-815
[51] Oyama T, Ran S, Ishida T, et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-KB activation in hemopoittic progenitor cells[J].J Immunol, 1998,160(3): 1224-1232.
[52] Mimura K, Kono K, Takahashi A,et al.Vascular endothelial growth factor inhibits the function of human mature dendritic cels mediated by VEGF receptor-2[J].Cancer lmmunol lmmunother,2007,56 (6):761—770
[53] Augustin H G. Antiangiogenic tumor therapy: will it work? Trends Pharmacol Sci. 1998,19(6):216-222
[54] Bont E S, Guikema J E, Scherpen F, et al. Mobilized human CD34~+ hematopoietic stem cell enhance tumor growth in a nonobese diabetic/severe combined immunodeficient mouse model of human non-Hodgkin's lymphoma [J]. Cancer Res,2001.61(20):7654-7659
[55] Wang L, Li L, Shojaei F, et al. Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties. Immunity,2004,21:31-41
[56] Schmeisser A, Garlichs C D, Zhang H,et al.Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions. Cardiovasc Res,2001,49:671-680
[57] Asahara T, Murohara T, Sullivan A, et al.Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997,275: 964-967
[58] Coukos G, Conejo-Garcia J R, Buckanovich R, et al. Vascular leukocytes: a population with angiogenic and immunosuppressive properties highly represented in ovarian cancer. Adv Exp Med Biol, 2007, 590:185-193.
[59] Fernandez Pujol B, Lucibello F C, Zuzarte M, et al .Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells. Eur J Cell Biol ,2001,80: 99-110
[60] Sozzani S, Rusnati M, Riboldi E, et al. Dendritic cell-endothelial cell cross-talk in angiogenesis. Trends Immunol. 2007,28(9):385-92