全球胃癌近半数发生在中国。肿瘤与支配神经的交互作用是近年来肿瘤研究的热点。国际抗癌联盟已将神经侵犯列入新版胃癌TNM分期系统，然而其机制仍不明确。故研究胃癌与迷走神经的交互作用的机制具有重要的意义。前期研究发现胃癌细胞表达M3受体，沉默M3的表达抑制胃癌细胞的增殖，诱导胃癌细胞的凋亡；M3在存在神经侵犯的人胃癌标本上呈异常高表达；且在小鼠胃癌原位移植模型上切断迷走神经左支能下调小鼠胃组织中M3基因的表达，并抑制小鼠胃粘膜的增殖和胃癌细胞的成瘤能力。据此假设：迷走神经和M3受体能调控胃癌的神经侵犯及发展进程。课题拟从临床、体外、体内三个层次利用组织芯片、细胞实验、动物模型、基因芯片、蛋白质组学等生物学研究手段揭示M3在胃癌的神经侵犯及与迷走神经交互作用中的机制。课题以期论证M3是联系胃癌和迷走神经的新桥梁，为探寻胃癌新的治疗思路和策略提供理论依据。

Nearly half number of global gastric cancer occurred in China. The interaction between tumor and the nerve innervated is the focus of cancer research in recent years. Union for International Cancer Control (UICC) has incorporated neural invasion into the new TNM (Tumor Lymph Node Metastasis) staging system for gastric cancer, but the underlying mechanism is still unclear. So, the study on mechanism underlying interaction between gastric cancer and vagus nerve is of great significance. Our previous study found that gastric cancer cells expressed M3 receptor, silence of M3 expression inhibited cell proliferation and induced apoptosis in gastric cancer cells, furthermore, M3 expression is increased in human gastric cancer with neural invasion. In addition, amputation of the left trunk of vagus nerve in a mouse gastric cancer xenograft model decreased M3 expression in mouse stomach tissue and inhibited tumor forming ability of gastric cancer cell. Accordingly, we make a hypothesis that vagus nerve and M3 receptors modulate neural invasion and development of gastric cancer. To test the hypothesis, we will use clinical trials, experiments in vitro and in vivo by several molecular biological research methods, such as tissue microarray, cell experiment, animal model, gene chip, proteomics. This study is aim to identify the role of M3 in the interaction between gastric cancer and vagus nerve and find a new bridge to communicate their signals. The study will provide a theoretical basis for understanding neural invasion and exploring new therapeutic strategy for gastric cancer.