细胞外基质刚度对宫颈癌细胞迁移的影响及分子机制

项目名称： 细胞外基质刚度对宫颈癌细胞迁移的影响及分子机制

项目编号： No.81472429

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： 耿力

作者单位： 北京大学

项目金额： 78万元

中文摘要： 宫颈癌的间质浸润和远处转移是临床治疗失败和影响预后的关键因素。细胞的迁移贯穿于肿瘤细胞浸润和转移的全过程, 研究表明，细胞外基质的力学性质是调控肿瘤细胞迁移的重要因素，但在不同肿瘤细胞，结论各异。细胞外基质刚度的改变是否影响宫颈癌细胞迁移至今尚未见报道。我们前期工作提示在较硬基底上培养的宫颈癌细胞多呈梭型，细胞骨架装配较完善，利于细胞迁移。本课题在此基础上，通过比较分析不同刚度基底上宫颈癌细胞的迁移特征，研究细胞外基质刚度对宫颈癌细胞迁移能力的影响。探讨细胞外基质刚度调控宫颈癌细胞迁移的分子机制，明确整合素受体以及Rho/ROCK信号通路在宫颈癌细胞感受力学信号从而改变生物学性质过程中的作用，本研究还将探索通过特异性阻断整合素受体和改变基底刚度来遏制宫颈癌细胞的迁移能力，为寻找阻止宫颈癌转移的新途径提供理论依据。

中文关键词： 宫颈癌；基底；刚度；迁移

英文摘要： Two key factors associated with the treatment failure and affecting the clinical prognosis of cervical cancer are cell invasiveness and metastasis. And cellular migration is involved throughout the entire process of tumor cell invasion and metastasis. Studies found that the mechanical properties of extracellular matrix (ECM) play an important role in the regulation of tumor cell migration，but researches with different cancers revealed different roles. With regard to cervical cancer, whether the stiffness of extracellular matrix could affect the migration of cells or not has not been reported. Our previous work showed that the morphology of cervical cancer cells cultured in hard matrix gel was fusiform and the cytoskeleton was assembled perfectly, which were conducive to migration. Based on this, the current study will analyze the migration characteristics of cervical carcinoma cells cultured in substrates of different stiffness, so as to explore the effect of stiffness of ECM on the migration of cervical cancer cells. Its underlying mechanism will be approached, clarifying the roles of integrin receptors and Rho/ROCK pathway in the change of the cellular biological characteristics with extra mechanical stimulation. In addition, this study will investigate if specific blocking of integrin receptor and the change of substrate rigidity help prevent the migration of cervical cancer cells, which may provide a theoretical basis for a new clinical method to block up metastasis in cervical carcinoma.

英文关键词： cervical cancer;matrix;stiffness;migration