构建微流控芯片仿生模型研究转移相关蛋白在肝癌侵袭转移中的作用及机制

项目名称： 构建微流控芯片仿生模型研究转移相关蛋白在肝癌侵袭转移中的作用及机制

项目编号： No.81471755

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： 王立明

作者单位： 大连医科大学

项目金额： 73万元

中文摘要： 肝癌侵袭转移是肝癌治疗的难点和瓶颈，转移相关蛋白参与的微环境变化与肝癌侵袭转移密切相关，本课题组在前期合作项目人类肝脏蛋白质组修饰谱研究（863计划）中，利用定量蛋白质组学技术规模化、高可信度的筛选出多个与肝癌侵袭转移相关的特异性蛋白，但其作用的确切机理尚不清楚。本研究拟利用微流控芯片组织工程学技术，依据体内细胞与细胞、细胞与微环境相互作用的特性以及流体学原理，设计和构建一个多单元集成、多通道连接的高通量的仿生芯片肝癌模型，模拟体内肝癌细胞的真实状况，动态实时的观察肝癌细胞侵袭转移的全过程，进一步筛选与验证肝癌侵袭转移相关蛋白的特异性及功能，探讨肝癌侵袭转移过程中相关特异性蛋白与肝癌微环境的关系及其在肝癌侵袭转移中的作用机制。旨在建立肝癌细胞侵袭转移研究的新方法，并探讨肝癌侵袭转移的分子机制，寻找肝癌侵袭转移的预测指标和干预治疗的靶点。

中文关键词： 微流控芯片；仿生肝；原发性肝癌；侵袭转移；肿瘤微环境

英文摘要： Invasion and metastasis are the main challenges in the treatment of primary liver cancer. It has been approved that metastasis-associated proteins may be involved in the changes of the hepatic tumor microenvironment, which are closely related to invasion and metastasis of liver cancer. In our previous research project Study on Proteomic Modification of Human Liver (863 Plan), we identified a number of specific metastasis-associated proteins by using quantitative proteomic technique. The research is conducted through a large scale data analysis and has high credibility. However, how these specific metastasis-associated proteins correlate the microenvironment of primary liver cancer and what effect of these proteins are on the process of invasion and metastasis remain unclear. Therefore, the purpose of our new study is to explore the relationship between specific metastasis-associated proteins and the microenvironment of primary liver cancer and to analyze the possible effects of the proteins on the process of invasion and metastasis. Our study is designed on the basis of the principles of fluid mechanics and the characteristics of the interaction between cells and cells, as well as the interaction between cells and microenvironment. Through tissue engineering technique, we will design and establish a multi-unit integrated, multi-channel connected, and high-throughput bionic chip liver cancer model to simulate the real condition of liver cancer cells. Then we may be able to watch the process of invasion and metastasis in a dynamic and real-time way. We will further screen and verify the specificity and function of metastasis-associated proteins of liver cancer in the process. Our research will establish a new method for analyzing invasion and metastasis of primary liver cancer. It will be also likely to provide a unique way for understanding the mechanism of invasion and metastasis on molecular level, and give us the predictive indicators for diagnosis and the useful information for the molecularly targeted therapy.

英文关键词： microfluidic chip;bionic liver;primary liver cancer;invasion and metastasis;neoplasm microenvironment