肿瘤转移的“种子和土壤”假说认为，转移的部位不是随机的，而是具有嗜器官性。肝转移是胃癌重要的转移形式之一，但发生机制仍不明朗。微囊泡(MV)由细胞主动分泌，可调控靶细胞的信号通路，但胃癌MV是否可以调控肝脏微环境来促进肝转移尚无报道。我们研究发现胃癌患者血清MV和胃癌细胞MV中均含有EGFR；并证明分泌型EGFR能由MV运输并定位到肝细胞膜上。进一步研究发现，运输到肝细胞的EGFR通过抑制miR-26，激活肝细胞生长因子（HGF）；而HGF是促进肿瘤增殖转移的重要因子，因而胃癌MV可以改造肝脏微环境。本课题拟证明肝细胞中上调的HGF具有促进血液中循环肿瘤细胞（CTC）在肝脏的“着陆”和生长；在体内和体外实验，证明被MV改造的肝脏微环境可以调节癌细胞生物学特征；并尝试探讨EGFR抑制miR-26表达的分子机理。本课题不仅揭示了胃癌肝转移的新机制，更为临床胃癌治疗提供了新方向。

According to the “seed and soil” hypothesis, tumor metastasis has organ specificity instead of irregularity. Liver metastasis is one of the main ways in the advanced gastric cancer; however, the detailed mechanism is still not clear. Microvesicles (MVs) are small particles that are secreted from cells, regulating the signaling pathways of targeted cells, but the function of gastric tumor derived MVs in promoting liver metastasis by reconstructing the microenvironment of liver has not been reported yet. We have found that the EGFR is highly expressed in the serum MVs of gastric cancer patients, as well as in the MVs secreted by gastric cancer cell line. This form of secreted EGFR is proved to be delivered by MVs and finally relocated in the outer surface of liver cell membrane. Subsequently, the up-regulated EGFR in primary liver cells activates HGF expression and paracrine by suppressing miR-26. HGF is well known to promote cancer cell growth and migration, thus gastric cancer MVs play a key role in regulating liver microenvironment. This project is designed to prove that the up-regulation of HGF in liver cells promotes the colonization and proliferation of CTC; and we will evaluate the function of liver microenvironment re-constructed by MV in regulating cancer cells; the molecular mechanism that EGFR suppresses miR-26 will also be explored. Our study will be important to reveal a novel mechanism of tumor metastasis; moreover, it provides a new direction and target for preventing the progress of gastric cancer.