胃癌是我国最常见的恶性肿瘤之一，其发病率高、预后差。肿瘤转移是胃癌患者的主要死因。上皮间质转化（EMT）和肿瘤微环境是肿瘤转移必要条件。Exosome（EXO)参与EMT发生，并调控肿瘤细胞与基质细胞交互对话，营造促癌微环境。分泌miRNA由EXO分泌至胞外，是细胞间交流的重要媒介。本课题组前期研究发现胃癌细胞分泌EXO富含多种miRNA，能促进成纤维细胞增殖和迁移并向肿瘤相关成纤维细胞（CAF）转化；CAF又可促使胃癌细胞分泌EXO并发生EMT。由此推测EXO传输miRNA可能为调控两者交互对话而促进肿瘤转移的元凶。本项目以胃癌细胞和CAF为切入点，分离纯化EXO并鉴定其功能性的miRNA。采用分子生物学、基因敲除、激光共聚焦、3D细胞培养等技术，从整体-细胞-亚细胞三个层次，探讨分泌miRNA调控胃癌细胞-基质细胞对话从而营造促癌转移微环境的分子机制，并为肿瘤诊断治疗提供新的靶位点。

Gastric cancer is one of the most common malignant tumors in China with high incidence of mortality and poor prognosis. Tumor metastasis is a major cause of death in patients with gastric cancer. Epithelial-mesenchymal transition (EMT) and metastatic niche formation are essential to tumor metastasis. It has been proved that exosomes (EXO) play a key role in EMT and regulate the cross-talk between tumor cells and stromal cells to create the metastatic niche. The secreted-miRNA is an important medium of intercellular communication and secreted to the extracellular through EXO. In the preliminary experiment, we found that gastric cancer cell-secreted EXO, rich in a variety of miRNAs, can promote fibroblasts proliferation, migration and transformation into cancer-associated fibroblas (CAF); CAF can promote the secretion of EXO and occurrence of EMT in gastric cancer cells in turn. Thus we speculate that the exosomal transfer of functional microRNAs may play a crucial role in cross-talk between gastric cancer and stromal cellls, and promote tumor metastasis. The project takes gastric cancer cells and CAF as the breakthrough point. We will separate EXO from gastric cancer cells and CAF, and identify the functional microRNAs. Using molecular biology method, gene knockout technique, Confocal microscopy scanning, 3D cell culture technology and etc, we plan to investigate the role and mechanism of secreted-miRNA that involved in the mutual interactions. This study will elucidate the molecular mechanism of secreted-miRNA though regulating intercellular communication, and leading to a favourable metastatic niche from a new perspective, which might provide new biomarkers and targets for the diagnosis and treatment of cancer.