胃癌MSC源性细胞因子调节Th17/Treg细胞分化作用机制及其临床应用

项目名称： 胃癌MSC源性细胞因子调节Th17/Treg细胞分化作用机制及其临床应用

项目编号： No.81472334

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 朱伟

作者单位： 江苏大学

项目金额： 70万元

中文摘要： 我们前期研究证实骨髓间质干细胞（BMMSCs）体内能促进肿瘤生长，并从人胃癌组织分离到胃癌间质干细胞（GC-MSCs），研究表明GC-MSCs具有较BMMSCs更强的促肿瘤生长能力。近期我们发现GC-MSCs具有诱导CD4＋T细胞向Th17细胞分化的能力，并发现胃癌病人肿瘤组织及外周血中Th17细胞及相关因子表达明显增多，表明Th17细胞与胃癌的发生发展密切相关。但胃癌微环境中GC-MSCs 与Th17细胞的作用机制及在胃癌发生发展中的作用还不清楚。本课题将采用Luminex芯片及细胞分子生物学技术筛选出GC-MSCs调节Th17/Treg细胞分化的关键因子及探讨其作用机制。体内外观察GC-MSCs诱导的Th17/Treg细胞在胃癌发生发展中的作用，并结合临床胃癌患者肿瘤组织及血浆（或exosomes）关键细胞因子的检测，评价其临床应用价值，为胃癌的诊断、预后判断和治疗提供新的分子标志。

中文关键词： C07_胃肿瘤；间质干细胞；Th17；分化；调节

英文摘要： We have previously demonstrated that bone marrow mesenchymal stem cells (BMMSCs) could promote tumor growth. We have also successfully isolated mesenchymal stem cells from gastric cancer tissue (GC-MSCs)which showed more potent than BMMSCs in promoting tumor growth. We recently found that GC-MSCs could induce the differentiation of CD4+ T cells into Th17／Treg cells in vitro, while the number of Th17 cells and the levels of related cytokines were also significantly increased in both tumor tissue and peripheral blood of gastric cancer patients, indicating that Th17 cells may associate with the development and progression of gastric cancer. However, the exact mechanism involving Th17 and GC-MSCs is unknown. In this project we will seek the key specific factors in GC-MSCs that induce Th17/Treg cell differentiation by using the Luminex assay,and other cellular and molecular biology approaches, and further delineate the mechanisms by which tumor growth is promoted . The effect of GC-MSCs induced Th17/Treg cells in gastric cancer will be investigated both in vitro and in vivo. Together with the detection of key cytokines in the tumor tissue as well as in blood circulation (or in exosomes), we will formulate a new panel of biomarkers, and evaluate their clinical values in diagnosis, prognosis and treatment of gastric cancer.

英文关键词： gastric cancer;mesenchymal stem cell;Th17;differentiation;regulation