我们前期研究发现肿瘤来源的Versican V1可以诱导髓系细胞分泌炎症因子促进肺癌增殖，但具体作用机制不清楚，并且其在肿瘤微环境中的表达调控机制不明。为此，本研究拟以髓系细胞RelA/p65敲除（NFkB信号抑制）的转基因小鼠为研究对象，通过尾静脉注射Versican V1上调/下调的LLC肺癌细胞建立NSCLC模型，研究Versican V1对小鼠NSCLC生长的影响和髓系细胞NFkB信号在其中的作用；随后借助芯片、Western Blot检测髓系细胞内重要信号分子和信号转导通路的表达与活化；进而利用质谱，ChIP，CO-IP，电泳迁移率试验、荧光素酶报告基因等细胞和分子生物学技术研究Versican V1激活髓系细胞NF-kB信号促进肺肿瘤增殖的分子机制及在肺肿瘤微环境中的表达调控机制。为阐明Versican V1的调控及在肺癌增殖的作用机制与临床应用价值提供实验依据。

Although we previously reported the tumor-derived Versican V1 can promotes the proliferation of lung cancer by induction of inflammatory cytokines in myeloid cells, the specific mechanism is not clear, and the expression regulation mechanism of Versican V1 in the tumor microenvironment remains unknown. First of all, this study is to investigate tumor growth promotion function of Versican V1 and the role of myeloid cell NFkB signaling in NSCLC transgenic mice with RelA/p65 knockout by tail vein injection of Lewis lung carcinoma cells with up/down-regulation of Versican V1 expression. Moreover, to analyze expression and activation of several important signaling molecules and signaling pathways in myeloid cells through chips and western blot. Finally, to research the molecular mechanisms of tumor promotion effect of Versican V1 in NSCLC through activating myeloid cell NFkB signaling, and the expression regulation mechanism of Versican.V1 in the tumor microenvironment via cellular and molecular biology techniques containing Mass Spectra, ChIP, CO-IP, EMSA, and Luciferase reportor assay etc. This study will provide an experiemental basis for elucidating the expression regulation and the mechanism of action in lung tumor proliferation of Versican V1 and its clinical applied value.