上皮间质转化—-CCL5促进乳腺肿瘤进展的可能的新机制

项目名称： 上皮间质转化—-CCL5促进乳腺肿瘤进展的可能的新机制

项目编号： No.81201524

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： 张岩

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： CCL5是应急过程中细胞分泌的趋化因子，在肿瘤（尤其是乳腺肿瘤）中高表达，与肿瘤的恶性进展密切相关，是肿瘤细胞发生侵袭和转移的主要原因。然而其促进肿瘤进展的机制仍不明确。EMT是上皮细胞肿瘤获得迁移和侵袭能力的重要生物学过程。但目前关于EMT介导CCL5促进乳腺肿瘤转移的机制却未见报道。我们前期研究发现CCL5缺失小鼠乳腺癌组织中EMT显著低于对照组，提示EMT可能参与CCL5介导的乳腺肿瘤的侵袭和转移。本课题拟采用4T1小鼠乳腺癌模型，探讨在乳腺肿瘤进展中CCL5对EMT的影响；并以CCL5蛋白诱导的人乳腺癌细胞MDA-MB-231为模型，体外探讨EMT在CCL5诱导的乳腺癌细胞侵袭过程中的必要性及CCL5调节TGF-β依赖的EMT的可能分子机制。本项目将为阐明CCL5促进乳腺肿瘤进展提供新的分子机制并为乳腺肿瘤的治疗提供新的靶标。

中文关键词： CCL5；Luminal型乳腺癌；上皮间质转化；肺转移；Th2型CD4+ T细胞

英文摘要： CCL5 is a chemokine produced by human cells in response to stress. It is overexpressed in a variety of tumors (especially in breast cancer), and it is highly related to tumor progress. CCL5 play an essential role in tumor cells' invasion and migration. However, the mechanism on how CCL5 promotes tumor progress is not very clear. EMT is an important biological progress for epithelial cancer cells to get the abilities of invasion and migration, but there is no report on the relationship between CCL5 and EMT. Our preliminary data found breast cancer EMT is inhibited in CCL5-/- mice compared to control mice, indicating that EMT maybe involves into CCL5-mediated breast cancer progress. In this project, we will utilize mouse 4T1 breast cancer model in Balb/C mice to explore the effect of CCL5 on EMT in progress of breast cancer metastasis. At the same time, we will use CCL5 protein-stimulated human breast cancer cell MDA-MB-231 to figure our the essential role of EMT in CCL5 promoting breast cancer cell invasion and migration and the molecular mechnism on how CCL5 regulates TGF-b dependent EMT. This project will find out the new mechanism on how CCL5 accelerates breast cancer progress and point our the new therapeutic target for treatment of breast cancer.

英文关键词： CCL5；luminal breast cancer；EMT；pulmonary metastasis；Th2 CD4+ T cells