FcγRIIa介导的血小板激活及KLF6在血小板促肝癌生长和转移中的作用及机制研究

项目名称： FcγRIIa介导的血小板激活及KLF6在血小板促肝癌生长和转移中的作用及机制研究

项目编号： No.81473270

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： 明章银

作者单位： 华中科技大学

项目金额： 70万元

中文摘要： 实验研究和临床观察均提示血小板是介导肿瘤转移的重要因素，血小板与肝癌细胞相互作用促进转移的分子机理仍不清楚。我们前期研究发现肝癌HepG2细胞可激活血小板，而激活血小板的上清液降低HepG2细胞中转录因子KLF6的表达，促进HepG2细胞增殖；使用FcγRIIa特异性抗体IV.3预孵育血小板后，其促进HepG2细胞增殖及降低KLF6作用消失。申请者推测肝癌细胞通过FcγRIIa激活血小板，激活后的血小板释放颗粒物质促进肝癌细胞增殖转移，该作用与肝癌细胞中KLF6相关。本课题采用不同转移潜能的肝癌细胞株、FcγRIIa特异性抗体及KLF6基因沉默和过表达方法研究血小板与肝癌细胞的相互作用；利用FcγRIIa转基因小鼠和检测肝癌患者血小板FcγRIIa磷酸化水平研究血小板FcγRIIa的作用，以揭示FcγRIIa和KLF6在血小板对肝癌增殖转移中的作用及分子机制，为肝癌防治提供新的思路和靶点。

中文关键词： 血小板；FcγRIIa；肝癌；KLF6；生长转移；分子机制

英文摘要： Clinical and experimental evidences support that platelet in the tumor microenvironment plays a crucial role in tumor growth and metastasis. But the mechanism of platelet interplay with hepatocellular carcinoma (HCC) is unclear. Our preliminary data implied that supernatant from activated platelets could reduce KLF6 expression in HepG2 cells and promote HepG2 cells proliferation. And platelets incubated with anti- FcγRIIa monoclonal antibody IV.3 abolished the effects. We speculate that platelet would promote the growth and metastasis of HCC through depressing expression of KLF6 by platelet granules releasing. We will explore the reciprocal effect between platelet and HCC cells with different metastasis capacity in vitro and in vivo. We will observe the effects of KLF-6 by its gene silence and overexpression. We also compare the phosphorylation of FcγRIIa between healthy people and patients with HCC. FcγRIIa transgene mice will be used to detect the effect of FcγRIIa in the reciprocal effect. All above would disclose the role of FcγRIIa and KLF6 in promoting HCC growth and metastasis as well as the molecular mechanism. And this would discover the new therapeutic targets for prevention and treatment of HCC.

英文关键词： platelet;FcγRIIa;hepatocellular carcinoma;KLF6;growth;metastasis;molecular mechanism