小胶质细胞M2型极化在胶质瘤EMT中的作用及分子机制研究

项目名称： 小胶质细胞M2型极化在胶质瘤EMT中的作用及分子机制研究

项目编号： No.81502552

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： 何蕾

作者单位： 中山大学

项目金额： 16.5万元

中文摘要： 目前认为上皮-间质转化（EMT）也存在于胶质瘤中，并和胶质瘤侵袭性相关，小胶质细胞（MG）作为中枢神经系统肿瘤微环境中最主要的免疫细胞，在胶质瘤EMT过程中的作用鲜有报道。我们前期研究发现MG和胶质瘤细胞共培养后，共培养体系中IL-10、TGF-β1浓度随时间持续增多，且MG向M2型极化，MG中miR-124表达下降，p-STAT3/STAT3增加，而胶质瘤细胞发生了EMT改变；进一步又证明TGF-β1诱导胶质瘤细胞发生EMT，转化后胶质瘤分泌IL-6明显增加。根据报道IL-6可以在肝癌中诱导miR-124下调及STAT3通路活化。故假设：胶质瘤微环境中小胶质细胞向M2型极化并介导胶质瘤EMT过程，胶质瘤细胞EMT后分泌细胞因子又促进MG向M2极化，形成一个正反馈环路。本项目拟明确MG向M2型极化与胶质瘤EMT的相关性，并深入探讨其分子机制，为胶质瘤防治新策略提供更多理论依据。

中文关键词： 小胶质细胞；极化；胶质瘤；上皮间质转化；STAT3；信号通路

英文摘要： Recent studies have demonstrated that epithelial mesenchymal transition (EMT) plays a critical role in human glioma and is tightly linked with the invasion of glioma cells. Microglia is the major proportion in the central nervous system tumor microenvironment. Effects and mechanisms underling microglia-mediated glioma EMT process are elusive. Our previous study found that the IL-10 and TGF-β1 increased with the time in the supernatant of microglia cocultured with glioma cells. Phenotype detection demonstrated the microglia polarized to M2 phenotype and the expression of p-STAT3/STAT3 increased in the microglia, whereas the miR-124 decreased. Meanwhile, the EMT was observed in glioma cells. Then glioma turned to EMT after TGF-β1 treatment and secreted IL-6 much more. The latter is the promoter of miR-124 and STAT3 signal pathway from the literature. Accordingly, we propose: microglia polarizes to M2 phenotype in glioma microenviroment and then induce glioma cells turn to EMT. EMT glioma cells induce microglia polarize to M2 phenotype. There is a positive feedback loop between M2 phenotype microglia and glioma EMT. We'll further explore the effects and mechanisms of microglial M2 polarization during epithelial mesenchymal transition in glioma. It is useful for understanding the invasive property of malignant gliomas and provide new theoretical basis to improve the curative effect of malignant glioma.

英文关键词： microglia;polarization;glioma;epithelial mesenchymal transition;STAT3 signal pathway