上皮-间质细胞转化（EMT）是胆管癌侵袭转移的核心环节，申请者前期研究表明aPKC-ι诱导胆管癌EMT。申请者近期发现，高表达aPKC-ι的肝内胆管癌细胞可促进血小板活化，而与血小板共培养后肝内胆管癌细胞aPKC-ι的表达显著上调。上述研究提示肝内胆管癌细胞可能通过aPKC-ι信号通路与血小板发生cross-talk。为了进一步明确分子机制，申请者利用细胞因子抗体芯片技术发现高表达aPKC-ι的肝内胆管癌细胞显著分泌PDGF-BB，且外源性PDGF-BB可诱导血小板活化。但PDGF-BB在体内主要来源于活化血小板，且申请者发现PDGF-BB可诱导肝内胆管癌细胞aPKC-ι、N-cadherin表达。申请者因此提出假说，aPKC-ι/PDGF-BB双向调控肝内胆管癌细胞与血小板间cross-talk,进而影响肿瘤EMT及血小板活化。本项目有望从新的角度阐明肝内胆管癌侵袭转移的调控机制。

Epithelial-Mesenchymal Transition is the core aspect of the invasion and metastasis in cholangiocarcinoma. In the previous studies, the applicant demonstrated that aPKC-ι could induce EMT in cholangiocarcinoma. Recently, the applicant found the intrahepatic cholangiocarcinoma cells with high level of aPKC-ι could promote platelet activation, and the expression of aPKC-ι in intrahepatic cholangiocarcinoma cells cocultured with platelet is increased. Based on the above research, it suggested that the intrahepatic cholangiocarcinoma cells had a cross-talk relationship with platelet through aPKC-ι signaling. For a further molecular mechanism, the applicant use the cytokine antibody microarray technology to find that the intrahepatic cholangiocarcinoma cells with high level of aPKC-ι could secret more PDGF-BB, and exogenous PDGF-BB could prompte platelet activation. But the PDGF-BB was mainly from activated platelets, and our research found the PDGF-BB could increase the expression of aPKC-ι and N-cadherin in intrahepatic cholangiocarcinoma cells. Therefore, the applicant propose a hypothesis that aPKC-ι/PDGF-BB regulated the cross-talk bi-directionally between the intrahepatic cholangiocarcinoma cells and platelet, then affect the process of EMT in tumor and the platelet activation. This project aim to elucidate the regulatory mechanism of invasion and metastasis in intrahepatic cholangiocarcinoma from a new perspective.