内皮祖细胞诱导肝细胞肝癌上皮间质转化及相关分子机制研究

项目名称： 内皮祖细胞诱导肝细胞肝癌上皮间质转化及相关分子机制研究

项目编号： No.81201621

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 余德才

作者单位： 南京大学

项目金额： 23万元

中文摘要： 内皮祖细胞（EPCs）在肿瘤转移与复发过程中扮演重要角色，说明EPCs直接或间接影响肿瘤生物学行为。我们先后证实EPCs参与构建肝癌微环境，促进肝癌发展与转移，且与其早期复发相关，但确切机理不明。在肿瘤进程中，肿瘤微环境诱导肿瘤细胞上皮间质转化（EMT），促进肿瘤转移。因此，作为肿瘤微环境重要成员，EPCs对肝癌EMT的作用值得研究。我们前期实验显示：EPCs分泌EMT相关因子，促进肝癌细胞迁移，并调节其EMT表型改变。我们假设：在肿瘤微环境中，EPCs通过诱导肝癌细胞EMT促进其转移。本课题通过体外和体内实验研究EPCs对肝癌细胞EMT及生物学行为的影响；体外模拟肿瘤微环境下EPCs对肝癌细胞EMT的作用；筛选EPCs诱导肝癌细胞EMT关键蛋白，并体外验证拮抗该类蛋白抑制肝癌转移。本研究首次阐明EPCs在肝癌细胞EMT过程中的作用及相关分子机制，为开发靶向肝癌关键分子的治疗手段打下基础。

中文关键词： 肝细胞肝癌；转移；微环境；内皮祖细胞；上皮间质转化

英文摘要： Endothelial progenitor cells (EPCs) play critical roles during tumor progression, metastasis, and recurrence, which support the idea that tumor biology is introduced directly or indirectly by EPCs. Our previous investigations showed that endothelial progenitor cells were mobilized and recruited into microenvironment in hepatocellular carcinoma (HCC) during tumor progression and metastasis, and were relevant to early recurrence of HCC. However, the exact mechanism remains unclear. The tumor microenvironment plays crucial role in facilitating cancer metastasis and may induce the occurrence of EMT in tumor cells. Given the close interaction between EPCs and cancer cells in the tumor environment, we asked whether EPCs might play critical roles in EMT in tumor cells or not. Our further investigations showed: 1, some cytokines relevant to EMT are secreted from EPCs; 2, the mobility of HCC cells is promoted and mesenchyme surfaces are up-regulated when HCC cells are co-cultured with EPCs. It is assumed that EPCs induce EMT of HCC cells, and promote HCC metastasis. The followings will be investigated in vitro and in vivo: 1, the surface markers and their relevant pathways of EMT and biological characters of HCC cells, co-cultured with EPCs, will be detected in vitro and in vivo. 2, EMT in HCC cells, co-cultured with EPC

英文关键词： hepatocellular carcinoma；metastasis；microenvironment；endothelial progenitor cells；epithelial mesenchymal transition