肿瘤血管生成与肝癌进展密切相关，但抗血管生成疗效不佳且有促肿瘤的反作用。除参与肿瘤血管生成外，肿瘤血管内皮细胞的主动促肿瘤作用更值得关注。研究表明肿瘤血管内皮细胞通过内皮间质转化（EndMT）促进了肿瘤进展，但在肝癌中作用不清。我们前期研究发现CD109在肝癌血管内皮细胞与正常血管内皮细胞存在差异表达，且肝癌血管内皮细胞CD109低表达与患者不良预后相关，我们证实肿瘤血管内皮细胞CD109低表达通过旁分泌IL-8促进了肝癌进展；同时我们也发现CD109低表达的血管内皮细胞外形从圆形铺路石样向长梭形转变，提示CD109低表达诱导了EndMT。本研究拟深入研究肝癌血管内皮细胞CD109表达下调诱导了EndMT，揭示CD109调控EndMT的关键机制，阐明EndMT在肝癌进展中的作用，并通过动物实验明确阻断CD109表达下调诱导EndMT对肝癌转移的作用，以期为肝癌转移的防治提供新的靶点。

Tumor angiogenesis plays an important role in hepatocellular carcinoma (HCC) progression, however anti-angiogenic therapies have poor efficacy and opposite effect to promote tumor progression. In addition to involved in tumor angiogenesis, tumor-associated endothelial cells (TEC) have been demonstrated to play more important active roles in tumor progression. Studies have shown that endothelial-mesenchymal transition (EndMT) of TEC promote tumor progression, but its role in HCC progression is unclear. Our previous work revealed that CD109 was one of differentiated expressed genes that determined TEC heterogeneity. The further study demonstrated that TEC with low CD109 expression were correlated with poor prognosis in HCC patients and CD109 knockdown TEC promoted HCC progression by paracrine interleukin-8 (IL-8) in vitro and in vivo. We observed that CD109 knockdown changed HUVEC shape from the rounded cobblestone-like morphology to an elongated spindle-like appearance, suggesting that CD109 knockdown might induce the EndMT of HUVEC. We aimed at verifying the effect of CD109 downregulation inducing the EndMT in HCC and unveiling its underlying mechanism through in vitro and in vivo experiments, further demonstrating the role of EndMT in HCC progression. The potential of inhibiting the EndMT to prevent the HCC metastasis in animal experiments may suggest the therapeutic targets for HCC.