IGFBP5促进非小细胞肺癌干细胞自我更新的功能及机制研究

项目名称： IGFBP5促进非小细胞肺癌干细胞自我更新的功能及机制研究

项目编号： No.81502565

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： 钱盈盈

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 肿瘤干细胞是非小细胞肺癌发生、转移及治疗失败的重要原因，靶向清除肺癌干细胞是改善患者预后的新的突破。为此我们通过建立原代肺癌细胞系，并用基因芯片筛选到肺癌干细胞自我更新潜在靶点-IGFBP5。IGFBP5与肿瘤发生发展关系密切，但在不同组织类型肿瘤中功能及作用机制不同，且在肺癌中研究较少，对非小细胞肺癌干细胞的调控方向及具体机制更是少有报道。我们在前期工作中发现IGFBP5在非小细胞肺癌干细胞中存在异常高表达并能调控肿瘤干细胞自我更新。本研究拟在前期基础上，通过体外克隆形成和体内致瘤等方法明确IGFBP5促进肺癌干细胞自我更新，运用高通量芯片分析及western blot等检测相关信号通路改变；进一步通过亲和串联质谱和蛋白-蛋白作用鉴定IGFBP5的下游靶蛋白，并收集肺癌标本分析其与肺癌预后的相关性。本研究将为非小细胞肺癌干细胞定向清除提供新的治疗靶点。

中文关键词： 非小细胞肺癌；肿瘤干细胞；自我更新；IGFBP5；靶向治疗

英文摘要： Non-small cell lung cancer (NSCLC) is a highly invasive type of cancer. Evidence suggests that lung cancer usually follows the cancer stem cell (CSC) model where a subset of cancer cells possess the capacity of self-renewal. Self-renewal is the breakthrough of CSCs-targeted therapy for lung cancer. By gene screening of primary NSCLC stem cells, we found a potential target of NSCLC stem cells --IGFBP5. Though IGFBP5 plays an important role in various types of cancers, studies on the role and molecular mechanisms of IGFBP5 in lung cancer are little. We previously found that IGFBP5 was aberrantly expressed in NSCLC stem cells and could promote the self-renewal ability of LCSCs. In this project we will employ sphere-forming assays and xenograft tumor assay to assess the role of IGFBP5 in the LCSC self-renewal ability, and analyze the signaling network of IGFBP5 with affymetrix geneship and western blot, and further identify the substrate for IGFBP5 promoting LCSCs self-renewal through TAP/MS analysis and protein-protein interaction assays. We will also collect NSCLC samples and clinical data to analyze the relationship of IGFBP5 with NSCLC prognosis. In this way, our study may provide a novel promising therapeutic target for NSCLC stem cells.

英文关键词： non-small cell lung cancer;cancer stem cells;self-renewal;IGFBP5;targeted therapy