COX-2/PGE2信号途径介导巨噬细胞极化与乳腺癌上皮间质转化交叉对话的分子机制研究

项目名称： COX-2/PGE2信号途径介导巨噬细胞极化与乳腺癌上皮间质转化交叉对话的分子机制研究

项目编号： No.81472475

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： 李洪忠

作者单位： 重庆医科大学

项目金额： 72万元

中文摘要： 肿瘤相关巨噬细胞（TAM）在乳腺癌发生发展中起着重要作用，但其在乳腺癌EMT中的作用及机制尚不明确，而乳腺癌EMT对巨噬细胞极化的影响也未可知。我们前期研究发现，TAM可促进乳腺癌EMT，而EMT可反向增强巨噬细胞向TAM极化，两个过程相互影响，协同促进乳腺癌恶性进程。综合文献资料和前期研究，我们推测COX-2/PGE2信号途径在巨噬细胞极化和乳腺癌EMT交互对话中扮演关键角色，两类细胞（TAM与乳腺癌细胞）中的COX-2/PGE2途径之间存在正性激活，共同释放的PGE2可分别通过各自细胞中EPs受体及相关信号通路促进巨噬细胞向TAM极化及乳腺癌EMT。为证实此假设，我们将通过临床标本、细胞共培养体系及动物模型，从分子、细胞和整体水平解析COX-2/PGE2信号途径介导此相互作用的分子机制。本课题可为肿瘤微环境研究提供新的思路，同时为COX-2抑制剂在临床肿瘤治疗中的应用提供新的实验依据。

中文关键词： C21_乳腺肿瘤；肿瘤微环境；上皮间质转化；巨噬细胞

英文摘要： Tumor -associated macrophage (TAM) plays an essential role in the development of breast cancer, however its effect and mechanism on EMT in breast cancer remains unclear, while the impact of EMT on macrophage polarization is also unknown. Our previous study showed that TAM promoted EMT in breast cancer, while EMT enhanced the polarization of macrophage to TAM, eventually promoting malignant process of breast cancer. Based on comprehensive literatures and our previous research, we supposed that COX-2/PGE2 signaling pathway played a key role in the interactive dialogue between macrophage polarization and breast cancer EMT. COX-2/PGE2 in TAM and breast cancer cells could positively activate each other, leading to PGE2 release which enhanced macrophage polarized to TAM and breast EMT through respective EP receptors and cell signaling pathways. In this study, clinical samples, cell co-culture system and animal models will be used to explore the molecular mechanisms of this interaction mediated by COX-2/PGE2. This study will provide a new idea for studying the tumor microenvironment, and new experimental evidences for the appliance of COX-2 inhibitors in clinical cancer therapy.

英文关键词： breast cancer;tumor microenvironment;epithelial-mesenchymal transition;macrophages