卵巢癌干细胞自分泌CCL5在肿瘤新生血管形成中的作用及机制研究

项目名称： 卵巢癌干细胞自分泌CCL5在肿瘤新生血管形成中的作用及机制研究

项目编号： No.31300647

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 龙海霞

作者单位： 中国人民解放军第三军医大学

项目金额： 25万元

中文摘要： 血管形成是卵巢癌发生、复发和转移的关键环节。我们前期发现：CCL5阻断后的卵巢癌干细胞（OCSCs）体内血管形成明显减少，体外向血管内皮细胞分化能力降低。基于CCL5能够活化NF-κB，并结合该信号通路在肿瘤血管形成中的重要作用，我们推测：OCSCs通过分泌高水平CCL5激活NF-κB信号通路，上调VEGF等促血管生成因子的表达，调控OCSCs分化成为血管内皮细胞，最终促进肿瘤的血管形成。本项目拟在前期工作基础上，采用化学阻断及特异性shRNA，明确NF-kB在CCL5介导OCSCs促卵巢癌血管生成中的作用；采用Western blot、ELISA及免疫荧光等方法探讨NF-kB促进OCSCs分化成为血管内皮细胞所调控的下游靶分子；临床标本分析OCSCs中CCL5表达与血管形成相关性及与患者预后的关系。通过本项目，不但能完善卵巢癌血管形成的分子机制，也将为临床卵巢癌抗血管生成治疗提供新靶点。

中文关键词： 卵巢癌；肿瘤干细胞；血管生成；CCL5；血管内皮细胞

英文摘要： Angiogenesis is involved in tumorgenesis, recurrence and metastasis for ovarian cancer. Our previous studies suggested that CCL5-knock down ovarian cancer stem cells (OCSCs) has less angiogenesis in vivo compared vector-transfected OCSCs, and the ability of differentiattion to vascular endothelial cells (VECs) was significantly reduced. Based on NF-κB signaling pathway activated by CCL5, combined with the biological function of NF-κB signaling pathway in tumor angiogenesis, we propose that OCSCs through secreting high level of CCL5, activate NF-κB signaling pathway,thereby regulating OCSCs differentiation into VECs, ultimately promote tumor angiogenesis.In this project, chemical blockers and specific shRNA silencing were used to observe the role of NF-κB in the CCL5 mediated OCSCs differentiate into VECs. Western blot,ELISA and other technology were used to explore the downstream target molecules of NF-kB to promote OCSCs differentiation into VECs.Clinical samples to further analyze the correlation of CCL5 and CD31, and the relatinship with the prognosis of patients.This project will not only benefit to understand the melecular mechanisms of ovarian cancer angiogenesis,but also provide new target for anti-angiogeneis therapy in the treatment of ovarian cnacer.

英文关键词： ovarian cancer；cancer stem cells；angiogenesis；CCL5；NF-kappa B