腹膜转移是胃癌患者失去根治手术机会和预后不良的主要原因，肿瘤微环境与肿瘤细胞相互作用在其中扮演关键角色。作为肿瘤微环境的重要组分，肿瘤相关成纤维细胞（CAFs）可释放包括趋化因子IL-8在内的分泌蛋白促进肿瘤细胞侵袭转移。我们前期研究发现，肿瘤相关成纤维细胞在胃癌组织中浸润显著增加，并与肿瘤浸润深度、淋巴结转移显著相关，而IL-8在胃癌的侵袭转移中发挥关键作用(Cancer Res, 2015)，其受体CXCR2在胃癌中提示患者不良预后(BMC Cancer, 2015)。本申请项目拟在前期发现基础上，阐述CAFs通过IL-8/CXCR2信号介导胃癌细胞失巢凋亡抵抗促进腹膜转移的分子机制和功能意义，建立CAFs与胃癌细胞相互作用促进胃癌腹膜转移的分子调控、生存评估、腹膜转移风险评估和治疗干预模型，为筛选肿瘤预后分子、开发阻断胃癌细胞与CAFs相互作用的靶向药物奠定扎实的理论基础。

Peritoneal metastasis is the main reason of unresectable gastric cancer, as well as dismal clinical outcome after surgery. Our previous work found that interleukin 8 participate in the invasion and metastasis of gastric cancer and high expression of its receptor CXCR2 was associated with unfavorable overall survival. As interleukin 8 was one of the canonical secretory phenotype, we found gastric cancer tissue was rich in fibroblasts and their distribution was associated withdepth of tumor invasion and lymph node metastasis. In the current project, we proposed to illuminate the molecular mechanisms, functional significance and interventive strategies of IL-8/CXCR2 positive feedback loop mediated anoikis resistance by CAFs in peritoneal metastasis of gastric cancer, so as to establish the model of molecular regulation, postoperative survival assessment, peritoneal metastasis risk prediction and interventive therapy based on the activation state of the feedback loop, which could help us lay the theoretical foundation for the development of diagnostic reagents and targeted therapeutic drugs.