胃癌微环境MSC调节中性粒细胞极化作用及分子机制

项目名称： 胃癌微环境MSC调节中性粒细胞极化作用及分子机制

项目编号： No.81201660

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： 张徐

作者单位： 江苏大学

项目金额： 23万元

中文摘要： 我们发现骨髓间质干细胞(BM-MSC)及其培养上清(CM)、分泌的微囊泡(MVs)可以在体内促进胃癌生长。我们从H. pylori阳性的胃癌组织中分离获得MSC, 并发现胃癌MSC较骨髓和癌旁组织来源的MSC更为活化，具有肿瘤相关成纤维细胞的性质。胃癌来源的MSC与胃癌发生和恶性转化的关系值得研究。本课题以胃癌来源MSC为研究对象，以中性粒细胞为切入点，研究在慢性炎症中MSC参与调节肿瘤微环境的作用。我们采用Luminex液相芯片筛选，在体外细胞模型和体内肿瘤模型中应用分子干预技术加以验证，确定胃癌MSC调节中性粒细胞促瘤表型极化的关键分子及其作用靶点。本研究将为阐明MSC在胃癌发生中的作用和分子机理提供新的证据，同时也为寻找新的胃癌治疗靶点提供实验依据，具有重要的科学意义。

中文关键词： 间质干细胞；胃癌；中性粒细胞；极化；

英文摘要： We have demonstrated that human bone marrow-derived mesenchymal stem cells (BM-MSC) and their derived conditioned medium and microvesicles can favor the growth of gastric cancer in vivo. We have recently isolated MSC-like cells from H. pylori-positive gastric cancer tissues and found that the gastric cancer tissue derived MSC are more activated than those from adjacent normal tissues and bone marrow, which possess the typical characteristics of carcinoma-associated fibroblasts (CAF). Thus, it deserves further investigation to elucidate the correlation between cancer derived MSC and cancer development and progression. This project is designed to study the roles of gastric cancer MSC in modulating tumor microenvironment, with special focus on tumor-associated neutrophils. Cytokine array will be performed to screen the differentially expressed cytokines and chemokines between gastric cancer and adjacent normal tissue derived MSC. The candidate cytokines and chemokines will be validated in in vitro cell model and in vivo animal model. The key molecules and signaling pathways by which tumor MSC-derived cytokines and chemokines mediate the polarization of neutrophils to acquire a protumor phenotype will be further investigated. The proposed study will help understand the roles and mechanisms of action of MSC in gastr

英文关键词： mesenchymal stem cells；gastric cancer；neutrophils；polarization；