细胞外基质蛋白CTHRC1在HPV16/18型宫颈癌微环境中的调控作用机制研究

项目名称： 细胞外基质蛋白CTHRC1在HPV16/18型宫颈癌微环境中的调控作用机制研究

项目编号： No.81472445

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： 张蓉

作者单位： 南方医科大学

项目金额： 78万元

中文摘要： 宫颈癌微环境通过多种方式引起癌细胞促进肿瘤生长、增殖、侵袭达到远处转移，但其作用靶点和发生机制尚不清楚。CTHRC1具有在宫颈癌微环境中辅助HPVE6/E7引起宫颈癌发生、促进肿瘤细胞生长、迁移、侵袭和转移等重要功能，我们分析其在宫颈癌的低分化、高侵袭、有淋巴结转移的组织中高表达，高表达CTHRC1的宫颈癌细胞能促进肿瘤细胞的迁移侵袭，且通过抑制经典的Wnt通路激活非经典的Wnt通路在启动宫颈癌的侵袭转移过程中起重要作用。我们前期已通过芯片技术分析宫颈癌临床样本及细胞株中CTHRC1表达，本研究拟对其进行蛋白纯化和制备单克隆抗体，用体内外共培养、动物活体成像和免疫共沉淀等等技术寻找相互作用受体，多方位对CTHRC1诱导宫颈癌细胞侵袭转移机制进行深入研究。本研究可望阐明宫颈癌微环境中高表达CTHRC1促进宫颈癌细胞侵袭的分子机制，为临床宫颈癌的综合治疗提供新的研究思路和治疗靶点。

中文关键词： C22_宫颈肿瘤；肿瘤微环境；CTHRC1；肿瘤治疗；HPVE6/E7

英文摘要： Microenvironment of cervical cancer through a variety of ways to promote tumor growth, proliferation, invasion and metastasis, but its targets and mechanisms of its occurrence is unclear. CTHRC1 assists with HPV E6/E7 in cervical cancer, promoting tumor cell growth, migration, invasion and metastasis, we demonstrated that CTHRC1 expression was significantly up-regulated in cervical cancer samples and was closely correlated with lower differentiation, higher invasion, positive lymph node, indicating a poor prognosis. Overexpression of CTHRC1 can promote cervical cancer cells migration and invasion, and this effect is related with inhibiting canonical Wnt pathway and activation of non-canonical Wnt pathway. In the previous study, we analyzed the expression of CTHRC1 in the tissue microarray of cancer samples and cell lines. Comprehensive investigations on detailed function and mechanism of CTHRC1 on tumorigenesis need future verification through multi-faceted, such as, analysis of clinical and pathological features, gene transfection (silence and over-expression) purification of recombinant proteins and monoclonal antibodies, in vitro co-culture and small animal imaging facility assay in vivo. Furthermore using the co-immunoprecipitation technique to find out the interaction receptors of CTHRC1 effected. The study is expected to clarify the molecular mechanisms of cancer microenvironment expression of CTHRC1 which will promote cancer cells invasion and indicate a potential therapeutic strategy for comprehensive treatment of cervical cancer.

英文关键词： cervical cancer;tumor microenvironment;CTHRC1;tumor treatment;HPVE6/E7