肝癌细胞和肝内胆管癌细胞并存、高转移率导致预后极差是混合型肝癌的两大特点。前期研究中我们发现，混合型肝癌中存在较高水平的肿瘤细胞上皮细胞-间充质转化（EMT）。进一步研究表明，肝内胆管癌细胞可诱导肝癌细胞发生EMT，并可能与肝内胆管癌细胞分泌Ln-332和TGF-β1相关。本研究拟在前期结果的基础上，深入研究肝内胆管癌细胞分泌Ln-332和TGF-β1对肝癌细胞增殖、迁移、侵袭及耐药的影响，明确肝内胆管癌细胞诱导肝癌细胞发生EMT的作用机制；利用混合型肝癌肺转移动物模型，证明肝内胆管癌细胞诱导肝癌细胞EMT与混合型肝癌易转移之间的联系。本研究是从新的角度研究混合型肝癌预后不良的原因，结果将为临床治疗混合型肝癌提供新的思路和可能的靶点。

Simultaneous containing hepatocellular carcinoma cells and cholangiocarinoma cells components, and metastatic feature are important characteristics of combined hepatocellular-cholangiocarcinomas. In the initial research period, we verified that high-level epithelial-mesenchymal transition (EMT) had arose in the combined hepatocellular-cholangiocarcinomas. Further study confirmed that cholangiocarinoma cells were able to induce hepatocellular carcinoma cells to arise EMT and the phenomenon might depend on Ln-332 and TGF-β1 which were secreted by cholangiocarinoma cells. On the basis of initial research, we will study the influence of Ln-332 and TGF-β1 to growth, migration, invasion and resistance of hepatocellular carcinoma cells, and clear the mechanism of EMT in hepatocellular carcinoma cells induced by cholangiocarinoma cells. We will also use a experimental lung metastasis model to determine the relation between the EMT in hepatocellular carcinoma cells induced by cholangiocarinoma cells and metastatic feature of combined hepatocellular-cholangiocarcinomas. Our research tries to explain the reason combined hepatocellular-cholangiocarcinomas has a dismal prognosis. It will offer a potential therapeutic approach for treatment of combined hepatocellular-cholangiocarcinomas.