应用微流控芯片仿生模型研究肺癌及其转移过程对微环境中间质细胞影响的分子机制

项目名称： 应用微流控芯片仿生模型研究肺癌及其转移过程对微环境中间质细胞影响的分子机制

项目编号： No.81330060

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 王琪

作者单位： 大连医科大学

项目金额： 290万元

中文摘要： 肺癌转移涉及一系列复杂的病理过程，与微环境密切相关。肺癌细胞一方面依赖微环境促进转移，另一方面又对微环境产生影响。明确肺癌及转移对微环境影响的分子机制，将有可能切断种子改造土壤的路径，为肺癌患者提供新的治疗靶点。但现有研究手段难以真实模拟肺癌微环境，其可靠性也有待提高。本课题组已利用微流控芯片技术模拟肺癌微环境，进行了肺癌个体化治疗、肺癌侵袭转移及肺部慢性炎症恶性转化等研究，本项目拟在此基础上，进一步构建仿生芯片肺生理模型、肺癌模型及脑、肝、骨等靶器官转移模型，在芯片平台再现肺癌发生及转移的病理过程；同时，利用芯片高通量、集成化优势，检测肺癌转移过程微环境中两大类主要间质细胞巨噬细胞和成纤维细胞的功能变化，明确肺癌转移影响微环境的分子机制，并通过动物实验对仿生芯片肺癌转移研究结果加以验证。该项目还将填补目前仿生芯片肺病理模型的研究空白，取代传统动物实验，为医学研究提供新的技术手段。

中文关键词： C05_气管；支气管；肺肿瘤;微流控芯片仿生模型;肺癌转移;肺癌微环境;分子机制

英文摘要： Lung cancer metastasis, which involves a series of complicated pathological process, is closely related to the tumor microenvironment. On the one hand, the microenvironment promotes lung cancer cells metastasis; on the other hand, lung cancer cells in turn affect the microenvironment. To confirm the molecular mechanisms of lung cancer and its metastasis impacting on microenvironment, will cut off the underlying pathways which involved in the improvement of seeds on the soil and thus may provide a novel therapeutic target for lung cancer patients. But now it is difficult to mimic the real lung tumor microenvironment depending on the existing research techniques, also the reliability needs to be improved. Before our group had successfully simulated the lung cancer microenvironment with microfluidic chip technology and applied it in many research fields such as individual treatment of lung cancer, lung cancer invasion and metastasis and the malignant transformation of chronic lung inflammation. Herein, based on the above new microfluidic platform, the project intends to construct a bionic microfluidic chip lung physical model, a bionic microfluidic chip lung cancer model and metastasis model including targeted organs brain, bone, liver etc in order to reproduce the whole pathological process of lung tumorgenesis and metastasis on the microfluidic chip. Simultaneously, to investigate the functional changes of main stromal cells macrophage and fibroblast submerged in the tumor metastasis microenvironment by means of the superiority of microfluidic chip high throughput and integration and further clarify the related molecular mechanisms of lung cancer metastasis impacting on microenvironment. Finally animal testing will be used to qualify the above results gained from the bionic microfluidic lung cancer metastasis model. What’s more, this project will fill the research blank of bionic microfluidic lung cancer pathological model and provide a new approach for medicine study instead of animal testing.

英文关键词： Tracheal bronchus lung tumors;Organs-on-microfluidic chips;Metastasis of lung cancer;Lung cancer microenvironment;Molecular mechanisms