炎症微环境下间充质干细胞调控肝癌干细胞干性维持的作用机制

项目名称： 炎症微环境下间充质干细胞调控肝癌干细胞干性维持的作用机制

项目编号： No.81502417

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 宗晨

作者单位： 中国人民解放军第二军医大学

项目金额： 18万元

中文摘要： 肿瘤微环境在肿瘤发生发展及放化疗抵抗方面具有重要作用。间充质干细胞作为一种基质细胞是肿瘤微环境的重要组成。我们前期研究发现炎症因子IFN-γ和TNF-α联合刺激的MSCs（IT-MSCs）具有促进肝癌化疗抵抗及增强肿瘤干细胞干性特征的能力，本课题拟体内外实验观察IT-MSCs对于肝癌细胞干性特征的影响并明确自噬对肝癌细胞干性的调控作用；利用过表达及shRNA技术调控自噬ROS/P38MAPK相关信号通路，阐释IT-MSCs介导的自噬调控肝癌细胞干性的分子机制；结合临床标本，分析肝癌微环境中MSCs数量、关键分子含量等与肝癌患者预后的相关性。本研究结果不但可加深对肿瘤微环境影响肿瘤发生及其化疗抵抗的理论认识，还可为判断肝癌化疗预后提供新指标，为肝癌的化疗联合治疗提供新靶点。

中文关键词： C09_肝和肝内胆管肿瘤；炎症微环境；间充质干细胞；肝癌干细胞；自噬

英文摘要： Tumor microenvironment play a vital role in the development of tumor and chemotherapy resistance. Mesenchymal stem cells are known as the important component of tumor microenvironment. Our previous studies showed that IFN-γ and TNF-α cotreated MSCs (IT-MSCs) could promote chemotherapy resistance of HCC and modulate the stemness of liver cancer stem cells. In this study, we intend to observe the effect of IT-MSCs on stemness of liver cancer stem cells and the regulation of autophay on stemness of liver cancer stem cells will be verified. Then, the mechanism of IT-MSCs involved autophagy regulating the stemness will be explored by modulating ROS/P38MAPK signaling pathway. Combining with clinical data, the correlation between content of MSCs, key factors and the prognosis of patients will be analyzed. The results of this study provide us a deeper understanding of the effect of tumor microenvironment on the development of HCC and its chemotherapy resistance, but also provide new prognostic markers for hepatocellular carcinoma chemotherapy, and new targets for combination therapy with chemotherapy.

英文关键词： hepatocellular and intrahepatic cholangiocellular carcinoma;inflammation environment;mesenchymal stem cells;liver cancer stem cells;autophagy