我们证明了HIV感染可诱导巨噬细胞分泌多种炎症因子杀伤神经元，然而这些因子另已知可促肿瘤细胞增殖、侵袭和迁移。HIV相关恶性肿瘤（HAM）中，肺癌发生率较正常人高3-4倍，且研究表明免疫缺陷和吸烟均不是其唯一病因。我们进而发现，携HIV gp120 DNA的小鼠骨髓来源巨噬细胞（BMM-gp120）可选择性将细胞增殖和F-actin合成相关蛋白输入肺癌A549细胞，并促其迁移表型。由此，我们提出HIV相关肺癌与艾滋病脑病可能存在某一类似机制，即携病毒基因的巨噬细胞。本项目拟先从gp120入手，以BMM-gp120分别作用于3种具不同迁移能力的肺癌细胞建立模型，以定性、定量蛋白质组学和生物信息学分析和预测BMM-gp120促肺癌细胞恶性表型的靶通路和靶蛋白。并在体外和小鼠体内模型中激动或阻断这些靶标，开展信号转导研究以确定机制。本项目有望首次从肿瘤微环境角度揭示HIV相关肺癌的新病因机制。

We have shown previously that HIV-1 infected macrophages secrete numerous neurotoxic cytokines and chemokines, however favorable for the proliferation, invasion and migration of tumor cells. In HIV-associated malignancies (HAM), HIV-1 associated lung cancer (HLAC) is a prevalent non-AIDS defining cancer with a 3-4 folds higher risk in the HIV-1 infected population, compared with the uninfected population. It was shown that both immunodeficiency and smoking can not solely responsible for this high risk, however HIV-1 is an independent factor. Our preliminary study indicated HIV-1 gp120 DNA containing bone marrow-derived macrophages (BMM-gp120) can selectively transport proliferation- and F-actin synthesis-relevant proteins in A549 lung cancer cells, accompanied by increased migration phenotypes. We therefore hypothesize HALC and HIV-1 associated neurodegenerative diseases share a similar etiologic factor, macrophages containing viral gene. To test this hypothesis, we will first focus on HIV-1 gp120, and establish investigative models by treating 3 thpes lung cancer cell lines with BMM-gp120, respectively. We will employ qualitative and quantitative proteomics to define the protein transportation and differentially expressed proteins in terms of BMM-gp120-mediated lung cancer cell malignant progression. With bioinformatics analysis, target pathways and proteins will be . Signaling transduction studies will then be performed by promoting and/or inhibiting these targets in both in vitro and in vivo models. This study possesses a potential to discover new etiological mechanism in HALC in terms of tumor microenvironment.