细胞外基质磷酸糖蛋白MEPE在前列腺癌骨转移过程中的作用及机制研究

项目名称： 细胞外基质磷酸糖蛋白MEPE在前列腺癌骨转移过程中的作用及机制研究

项目编号： No.31471312

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 刘爽

作者单位： 佳木斯大学

项目金额： 85万元

中文摘要： 前列腺癌是老年男性高发肿瘤，发病隐匿，易发骨转移。我们在前期工作中发现SBLINGs蛋白家族中MEPE蛋白在前列腺癌组织与骨转移灶中高表达，而在癌旁组织与前列腺增生组织中表达量极低。划痕实验与Transwell实验发现过表达MEPE蛋白细胞株迁移与侵袭能力增强，并伴有Integrin β1和BMP-2表达平行升高。本课题旨在研究MEPE蛋白促进前列腺癌骨转移的机制：1.明确MEPE蛋白在前列腺癌骨转移中的关键作用；2.分析MEPE蛋白与Integrin β1之间的作用机制，以及在Integrin β1/FAK/Src信号通路中的位置。3.明确MEPE蛋白在BMP-2/SMADs信号通路与经典Wnt通路cross talking的位置，确定其在骨转移灶形成的作用机制。4.分泌蛋白MEPE易在血清中检测，分析其与患病类型、转归的关系，评估其作为前列腺癌骨转移标记蛋白的临床应用价值。

中文关键词： 细胞外基质磷酸糖蛋白；前列腺癌；肿瘤转移

英文摘要： o Prostate cancer (PCa) is a high incidence cancer in the older men. PCa has few specific symptoms, early prostate cancer bone metastasis (PCaBM), and a poor prognosis. Matrix Endocellular PhosphoglycoprotEin(MEPE) is a member of Small Integrin-Binding Ligand N-linked Glycoproteins(SIBLINGs). Data shows us that mepe is expressed at high level in the primary focus and bone metastasis sample, while expressed at low level in adjacent tissue and benign prostate hyperplasia (BPH) tissue. We noted that over expressing MEPE can significantly increase cell migration and invasion in LNCaP prostate cancer cells by the Wound Heal assay and Transwell assay. At same time we detected the expression of Integrin β1 and BMP-2 increased simultaneously. In this project, we aim to investigate relationship between MEPE and PCaBM: 1.To comfirm the role of MEPE in PCaBM; 2.To confirm the interaction of MEPE with Integrin β1 to explore the regulation mechanism for pathway Integrin β1/FAK/Src. 2.To investigate the location of MEPE in cross talking of BMP-2/SMADs pathway and Wnt pathway and the molecular mechanism of metastasis in prostate cancer cells. 4. To evaluate the application value of MEPE as clinical diagnosis marker of PCaBM, we design a series of experiments in vivo and in vitro. We suppose that MEPE maybe a protein marker for PCaBM diagnosis.

英文关键词： MEPE;prostate;metastasis