20年来针对"种子-癌细胞"的"毒性"治疗效果差，迫使转向"土壤-肿瘤微环境" 寻找新的突破点。癌相关成纤维细胞（CAFs）是肿瘤微环境的主要成分， CAFs表型转换与肿瘤演进相互作用，而CAFs表型转换规律及机制均不清楚。拟在前期工作基础上，结合自身临床标本优势和肺腺癌演进阶段性强的特点，应用组织芯片研究CAFs表型转换与肺腺癌演进（时相性）的关系，并分析不同部位CAFs表型变化（空间特性）与癌进展的影响。应用原代细胞分离和细胞共培养技术，分析CAFs与癌细胞相互作用的机制及对生物学特性的影响；动物实验分析体内CAFs对肿瘤生长及转移的影响；western blot检测二者Cross-talk相关信号传导通路关键酶活性；体内、外应用阻断剂证实CAFs对肿瘤生物学特性的影响。旨在达到阐明CAFs表型变化规律及其与肺腺癌演进的分子机制。不但能揭示肺腺癌的发生机理，也能发现肺腺癌治疗的新靶点。

Last twenty years, it is the direction that the poor effect of target tumor cells(the seeds) alter to seek new methods on the tumor microenviorment(the soils). Cancer-associated fibroblasts (CAFs) are the primary cell type in the TME. But it is unknown that the mechnism of CAFs phenotype conversion and interaction with cancer cells. We aimed to investigate the Interaction between phenotype conversion with timing and spacial in cancer-associated fibroblasts and Lung Adenocarcinoma progressively development. The tissure array ,co-cell culture , western blot ,in vitro and in vivo experiment was applied to detect the phenotype change of CAFs and lung adenocarcinoma , the tumor growth and lung metametasis was investigatec.these results may illustrated the mechnism of lung cancer developed and found the new therapy target.