肝内复发是肝癌术后复发的主要形式，提示肝脏是适宜肝癌细胞转移的最适“土壤”。上皮-间质转换（EMT）赋予肿瘤远处转移的能力，但播散的肿瘤细胞在靶器官内滞留后，需要重新获得上皮细胞样表型，即发生EMT的反向过程“间质-上皮转换（MET）”才能进一步长成临床有意义的转移灶。我们发现，四氯化碳预处理裸鼠，肝脏内的星状细胞被激活，其表达的骨膜蛋白显著升高；经脾脏注射肝癌细胞后，与对照组相比，肝内出现更多的转移灶。我们推测，活化的星状细胞及其分泌的骨膜蛋白参与并改造了肝组织微环境，促进了肝癌肝内转移。本项目中，我们拟进一步研究：（1）MET转换在播散肝癌细胞进展为大体转移灶过程中的关键作用；（2）活化的星状细胞促进肝癌细胞MET过程的分子机制，特别是星状细胞来源的骨膜蛋白调节肝癌细胞MET过程的核心机制。通过揭示其中的关键机制，为肝癌术后的转移复发提供潜在的干预手段。

Intrahepatic recurrence is the main form of the post-operative recurrence of hepatocellular carcinoma (HCC), suggesting that the liver is the most appropriate "soil" suitable for the metastasis of hepatoma cells. Epithelial-mesenchymal transition (EMT) conferred the ability of tumor to distant metastasis, but the disseminated tumor cells (DTCs) were latent in the target organ. DTCs need to regain the epithelial cell-like phenotype, that is, they may reverse the process of EMT via a "mesenchymal-epithelial transition (MET) "to further grow into the clinical macrometastases. Previously, we found that in the tetrachloromethane pretreated nude mice, abundant hepatic stellate cells were activated, the expression of periostin was significantly increased; after injection of hepatoma cells into the spleen, more metastasis foci were observed in the pretreated group, compared with the control group. We speculated that the activated stellate cells and secreted periostin involved in the transformation of the liver microenvironment, contributing to the pre-meatastatic niche for HCC metastasis. In this project, we proposed to further study: (1) MET was the key process of the disseminated hepatoma cells growed into the macrometastases; (2) unveiled the mechanism how activated hepatic stellate cells induced the hepatoma cells underwent MET, especially the role of secreted periostin in regulating MET in hepatoma cells. By revealing the key mechanism and key molecules, we aimed to provide the potential intervention for the post-operative recurrence.