基于微流控芯片平台研究CXCL12-CXCR4信号对乳腺癌干细胞转移的影响

项目名称： 基于微流控芯片平台研究CXCL12-CXCR4信号对乳腺癌干细胞转移的影响

项目编号： No.81502579

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 侯志杰

作者单位： 大连医科大学

项目金额： 18万元

中文摘要： 实时动态检测肿瘤细胞转移是微流控芯片平台的主要优势。CXCL12-CXCR4信号介导干细胞迁移与归巢，提示CXCL12-CXCR4可能参与乳腺癌干细胞的转移。但目前尚无手段实现实时监测乳腺癌干细胞的迁移。申请人前期发现靶向乳腺癌干细胞可同时抑制乳腺癌的转移（Oncotarget，2015，已接收），并成功构建多种微流控芯片转移模型，用于模拟肿瘤微环境中不同因素对转移的影响。在此基础上，应用微流控芯片平台，本课题旨在探索1) CXCL12在三维培养条件下对乳腺癌干细胞转移的影响；2）明确CXCL12能否通过CXCR4受体诱导肿瘤干细胞发生上皮间质转化，进而增强其转移和侵袭能力，从而系统阐明CXCL12-CXCR4信号调控乳腺癌干细胞转移的分子机制。我们还将在肿瘤病人标本和动物模型中进一步验证CXCL12-CXCR4信号对乳腺癌干细胞转移的影响，为靶向乳腺癌干细胞，抑制肿瘤转移提供新的思路。

中文关键词： C21_乳腺肿瘤；微流控芯片；肿瘤干细胞；转移

英文摘要： Real-time and dynamic monitoring tumor cell metastasis is the main advantage of microfluidic platform. CXCL12-CXCR4 signaling mediated stem cell migration and homing, indicating CXCL12-CXCR4 signaling was related with breast cancer stem cell metastasis. However, there is no method to real-time monitor breast cancer stem cell migration. Our preliminary studies revealed that targeting breast cancer stem cells inhibited breast cancer metastasis (Oncotarget, 2015, accepted). In order to mimic the effect of factors in microenvironment on breast cancer cell metastasis, we successfully established several microfluidic chips for cancer metastasis study. By using microfluidic device, the aims of this study are to 1) investigate the chemotaxis of breast cancer stem cell to CXCL12 in three-dimensional culture conditions and 2) examine whether CXCL12-CXCR4 interaction enhance the migration and metastasis capability of breast cancer stem cells via inducing epithelial-mesenchymal transition. We will further explore the effect of CXCL12-CXCR4 on breast cancer stem cells in both tumor patient specimens and animal models. This study helps to advance our understanding of the mechanism of CXCL12-CXCR4 signaling regulating breast cancer stem cell metastasis and sheds light on targeting breast cancer stem cell and inhibiting cancer metastasis.

英文关键词： breast cancer;microfluidic device;cancer stem cell;metastasis