慢性炎症是癌症的重要发病机制之一。“炎-癌”转变的分子机制是当前肿瘤学研究的热点之一。S100A4是一种钙结合蛋白。前期研究表明S100A4能招募巨噬细胞促进皮肤癌的发生发展并参与肝纤维化及肝癌的发展。消除结肠中S100A4阳性细胞，结肠炎症反应明显减弱。然而S100A4如何参与结肠炎症反应，影响结肠癌发生的机制目前尚不清楚。. 本项目拟鉴定肠道炎症反应中S10A4阳性细胞的来源和类型；利用S100A4基因敲除小鼠，在体内特异性消除S100A4，采用AOM/DSS诱导的结肠癌模型，检测S100A4在结肠炎及结肠癌发生中的作用；结合体外实验，在细胞、分子水平分析S100A4与肿瘤细胞的相互作用，阐明其影响结肠炎相关的肿瘤发生的分子机制，为临床肿瘤的诊断和治疗提供新策略。

Chronic inflammation was contributed to the development of cancer. Many studies about the molecular mechanism are carried out today. S100A4, belongs to the S100 superfamily of calcium-binding proteins. We have previously reported that S100A4+ cells promoted skin tumor development via recruit macrophages.S100A4 also promoted liver fibrosis and hepatocarcinogenesis. Selectively deplection of S100A4+ cells in intestine, the level of inflammation decreased obviously. However, it is still not known how S100A4 regulate colon inflammation and tumorigenesis. . We will identify the origin and cell type of S100A4+ cells in colon during the process of inflammation; By using S100A4 KO mice ,depletion of S100A4, study the role of S100A4 in chronic inflammation in colon and in the process of tumorigenesis with AOM-DSS model. Analyze the interaction between S100A4 and tumor cells in vitro，elucidate related molecular mechanism. These studies will provide new strategy for clinical diagnosis and anti-cancer treatment.

S100A4是钙结合蛋白家族成员之一，在肿瘤转移过程中发挥重要作用，但它在调节炎症及结肠炎相关的肿瘤发生中的作用并不清楚。本项目采用AOM/DSS诱导的结肠炎相关的肿瘤模型发现结肠炎及结肠癌组织S100A4表达明显上调。S100A4-TK小鼠条件性敲除增殖的S100A4阳性细胞和全身敲除S100A4小鼠，结肠癌肿瘤的发生明显降低。S100A4敲除小鼠DSS诱导的结肠炎及巨噬细胞的浸润、细胞因子水平明显降低。进一步研究表明S100A4敲除后巨噬细胞的NF-κB信号通路减弱从而影响结肠炎症反应及肿瘤发生。该结果表明S100A4能通过促进炎症反应促进结肠癌的发生。阻断S100A4有可能会降低结肠炎相关的结肠癌的发生。