微环境介导血管生成日益成为肿瘤病因学的研究热点。我们前期研究发现肺癌细胞可以分泌微囊泡(MV),且含有AEG-1的MV可以被微血管内皮细胞(MEC)吞饮,进而调控MECs的生物学行为。本课题拟利用具有从支气管粘膜增生、鳞状化生、不典型增生、原位癌到浸润癌的肺癌模型，结合显微切割等技术，检测AEG-1对MECs基因表达谱和血管生成的动态调控。采用细胞共培养和血管生成试验等实时观察MV的超微结构及对MEC生物学行为的影响；结合质粒转染、RNA干扰和GST-pull down技术，探究JAK/STAT通路在AEG-1调控MECs生物学行为进而介导血管生成的分子机制,明确AEG-1直接作用的靶蛋白,探明AEG-1/JAK/STAT下游直接调控的血管生成因子，为肺癌靶向治疗提供依据。结合临床组织和血液标本，利用SVM模型分析AEG-1等基因与临床病理参数的关系，为肺癌早期诊断、复发和预后判断奠定基础

The research on angiogenesis mechanism mediated by microenvironment is a promising branch of cancer itiology. Our prior research has showed that AEG-1(Astrocyte Elevated Gene-1) has the abilitity to regulate the biological behavior of MEC(Microvascular Endothelial Cell). Firstly, lung cancer cells secrete microvesicles with AEG-1. Then, microvesicles with AEG-1 can be engulfed by MEC, through which AEG-1 enters into MEC and plays a vital role in angiogenesis.This study combines microdissection technology with the lung cancer model, which displays diverse lesions including hyperplasia of bronchia mucosa, squamous metaplasia, atypical dysplasia, carcinoma in situ and infiltrating carcinoma, to explore how AEG-1 dynamicly regulate the gene expression profile of MEC and tumor angiogenesis. Simultaneously,we utilize cell co-culture and angiogenesis assay to observe the ultrastructure of MVs and their influence on the biological behavior of MECs. Combining plasmid transfection, RNA interference with GST-pull down technology, we explore the molecular mechanism about JAK/STAT pathway through which AEG-1 regulates the biological behavior of MECs and further mediates angiogenesis. Related assays were devised to search for the specific target protein with which AEG-1 interact, and angiogenesis factors being downstream of AEG-1/JAK/STAT in order to provide experimental basis for target therapy of lung cancer. Eventually, basing on tissue and blood samples,we analyze the correlationship between various genes and clinical pathology parameters utilizing SVM (Support Vector Machine）to provide scientific data for the early diagnosis, recurrence and prognosis of lung cancer.