血小板上调乳腺癌细胞膜的整合素表达进而促进癌细胞转移的分子机制研究

项目名称： 血小板上调乳腺癌细胞膜的整合素表达进而促进癌细胞转移的分子机制研究

项目编号： No.81201656

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 柳杨

作者单位： 大连医科大学

项目金额： 23万元

中文摘要： 转移是乳腺癌治疗失败的主要原因，血行转移是乳腺癌转移的重要途径之一。动物实验证实小鼠晚期的乳腺癌组织中有大量的血小板聚集。临床研究也发现乳腺癌转移患者的血小板数量及活化程度都显著提高。这些现象提示血小板可能参与癌症转移。申请者前期工作中发现活化的血小板可通过其表面的P-selectin与单核细胞表面的糖蛋白PSGL-1结合，进而上调单核细胞表面β整合素的表达，加速单核细胞的侵润能力（ATVB，2011，31：834）。在此基础上，运用细胞生物学及蛋白组学等方法，本课题旨在探索1）血小板与培养的乳腺癌细胞株能否通过P-selectin和PSGL-1结合；2）该结合能否引起癌细胞表面整合素的上调进而增强癌细胞的粘附，迁移和侵润能力，从而系统的阐明血小板促进癌细胞转移的分子机制。我们还将利用裸鼠乳腺癌转移模型进一步验证抗血小板干预对癌细胞转移的影响，为开发抑制癌症转移的药物提拱新途径。

中文关键词： 血小板；肝细胞癌；分化；氯吡格雷；

英文摘要： Breast cancer is the most common malignant disease in women. In these patients, it is not the primary tumor, but its metastases at distant sites via bloodstream that are main cause of death. In clinics, cancer patients who developed distant metastasis displayed abnormal platelets in both count and activity, indicating that platelets might contribute to the development of metastasis. The investigator has shown that platelets are able to bind monocytes via P-selectin (on platelets) and its ligand P-selectin glycoportein ligand (PSGL)-1 (on monocytes) upon platelet stimulation. Such an action would lead to monocytes activation, with an up-regulation of monocyte membrane β integrins as an imporant mechnisam (ATVB，2011，31：834). By using breast cancer cell lines and the mouse model of breaset cancer metasists, the aims of this study is 1) to investigate whether platelets can bind with breast cancer cells via P-selectin and PSGL and 2) the mechanism and role of platelet-cancer cell interaction in the progress of breast cancer metastasis, as well as the efficacy of anti-platelet interventions. This study help to advance our understanding of the mechanism of cancer metastasis via bloodstream and sheds some light on a future research area investigating the potential use platelets as an attractive therapeutic target or met

英文关键词： Platelet；Hepatocellular carcinoma；differentiation；clopidogrel；