促血管生成相关因子及其受体、MMPs受IL-17RA调控影响非小细胞肺癌进展的作用机制研究

TH17细胞分泌的IL-17能够刺激多种正常细胞产生促血管生成因子及基质金属蛋白酶（MMPs）。我们的前期研究发现非小细胞肺癌（NSCLC）癌组织中IL-17表达与肿瘤血管密度、MMP9的表达呈正相关，而且是影响预后的独立因素。故推测IL-17在肿瘤发生、发展中起到重要作用，但IL-17膜受体IL-17RA在NSCLC生长、迁移、侵袭中的调控机制尚未明确。因此本课题拟通过慢病毒质粒GV248构建稳定干扰和过表达IL-17RA的NSCLC细胞株，探讨:IL-17RA对NSCLC细胞分泌促血管生成趋化因子及C57BL/6小鼠体内移植瘤生长的影响；IL-17RA对NSCLC细胞的迁移侵袭能力的影响，进一步明确受IL-17RA调控的MMPs，阐明其调控机制。本研究将有助于我们深入了解IL-17RA在肿瘤发展中的作用，为NSCLC靶向治疗提供新的思路。

IL-17 secreted by TH17 cell can stimulate various normal cells to product angiogenic factors and MMPs. We found that the expression of IL-17, in NSCLC tumor tissue, was closely related to intratumor vascular density and the expression of MMP9, and it was the independent factor of NSCLC patient's prognosis. IL-17 plays an important role in the tumor development. However, the mechanism of IL-17 receptor IL-17RA in NSCLC cell growth，migration and invasion is still obscure.Therefore，in this study,firstly we will build the stable overexpression and downregulation of IL-17RA in NSCLC cell lines by lentivirus plasmid GV248. Secondly,we will investigate the influence of IL-17RA against the angiogenesis factors secreted by high/low expression of IL-17RA NSCLC cells,evaluate the affection of xenograft growth in C57BL/6 mice.Finaly,we will investigate the influence of IL-17RA against the migration and invasion in high/low expression of IL-17RA NSCLC cells, explore the related MMPs modulated by IL-17RA,illuminate the regulation of related signaling pathway.This subject might provide insights into the role of IL-17RA in tumor development and novel targeted therapy for NSCLC.