Establishment of a novel rat cholangiocarcinoma cell culture model.

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Abstract
Furan cholangiocarcinogenesis in rat liver is proving to be a unique and useful animal model for investigating important aspects of the cellular and molecular pathogenesis of cholangiocarcinoma potentially relevant to the human disease. We now describe the first culture model of rat cholangiocarcinoma cells derived from a transplantable cholangiocarcinoma originally induced in the liver of a furan-treated rat. An epithelial cell isolate highly enriched in viable cholangiocarcinoma cells was consistently obtained from transplantable cholangiocarcinoma tissue utilizing a similar procedure to that recently developed by us to establish a new rat hyperplastic bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro . Primary cholangiocarcinoma cell cultures could be readily established with these isolated cells and, in addition, we established from one such culture a novel rat cholangiocarcinoma cell line designated C611B. Cultured C611B cholangiocarcinoma cells retained a number of important characteristic features of the carcinoma cells of the parent tumor, including marked expression of the tyrosine kinase growth factor receptor proteins c-Met and c-Neu. Under basal culture conditions, the C611B cell line exhibited a cell doubling time of ~24 h and was aneuploid, with a predominant chromosomal count of 43. Moreover, C611B cells on collagen gels were 100% tumorigenic when transplanted into inguinal fat pads of syngeneic rats. All tumors formed at the transplantation site were cytokeratin 19-positive, mucin-producing tubular adenocarcinomas whose histological and phenotypic features closely resembled those of the furan-induced parent transplantable rat cholangiocarcinoma. Based on our findings, we believe that this novel rat cholangiocarcinoma cell culture model can serve as a valuable resource for investigating aberrant growth properties and tumor progression in biliary cancer.