CD40信号促进脑胶质瘤干细胞向内皮细胞分化形成肿瘤新生血管的作用及机制

项目名称： CD40信号促进脑胶质瘤干细胞向内皮细胞分化形成肿瘤新生血管的作用及机制

项目编号： No.31200661

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 葛彦

作者单位： 苏州大学

项目金额： 25万元

中文摘要： 脑胶质瘤是中枢神经系统最常见的恶性肿瘤，易复发、预后差与其浸润性生长依赖新生血管形成密切相关。最新研究显示：肿瘤干细胞是肿瘤新生血管的重要来源。课题组前期工作建立了一株干细胞样胶质瘤细胞株，发现通过激发其表达的CD40分子，可促进肿瘤血管形成，但确切的机制尚待研究。鉴此，本项目以肿瘤微环境中重要的促血管因子CD40为切入点，以胶质瘤干细胞为研究对象，从分子、细胞和动物实验等多个层面开展：一方面，探讨CD40信号如何参与胶质瘤干细胞向内皮祖细胞分化，并通过刺激何种促血管因子分泌促进肿瘤微血管新生，阐明CD40信号在胶质瘤新生血管形成中的作用；另一方面，通过胶质瘤干细胞内CD40信号转导通路的研究，揭示CD40信号调节胶质瘤干细胞向内皮细胞分化的内在机制，筛选关键分子作为靶向治疗的候选靶点；在此基础上，利用小鼠荷瘤模型实验性治疗并验证体外实验结果，以期为靶向肿瘤干细胞的抗血管治疗提供新思路。

中文关键词： 脑胶质瘤；肿瘤干细胞；肿瘤微环境；CD40；血管形成

英文摘要： Glioblastoma(GBM) is among the most aggressive and highly angiogenetic malignancy of human cancers. The mechchanisms of angiogenesis and the orgin of tumor endothelial cells remian poorly defined, which limited the application of anti-angiogenesis therapy of tumor. Very recent research showed that glioma stem-like cells give rise to tumor endothelium. Interaction and mutual support between tumor cells and microvessels inside stem cell vascular niche contribute to immune escape of tumor. In our previously study, we have established a CD133+ glioma stem cell line expressing high level of CD40 which was proved to be crucial in agiogenesis of glioma. To further explore the mechanism of tumor stem cell differentiation into endothelial progenitor, our research is to focus on CD40, a very important proangiogensis factor in tumor microenvironment and its biofunction on glioma stem cells. To investigate the function of CD40 signaling on the formation of abnormal vasculature, the following experiments should be inclued: the role of CD40 signaling on differentiation of glioma stem cells to endothelial progenitors; on secretion of proangiogensis factors promoting agiogenesis of glioma. Through signal pathway investigation, some crucial molecules on the pathway should be selected as key regulatory targets. On the basis of in

英文关键词： glioma；cancer stem cell；tumor microenviornment；CD40；agiogenesis