Establishment of a novel rat cholangiocarcinoma cell culture model

Furan cholangiocarcinogenesis in rat liver is proving to be a unique and us eful animal model for investigating important aspects of the cellula rand m olecular pathogenesis of cholangiocarcinoma potentially relevant to the hum an disease. we now describe the first culture model of rat cholangiocarcino ma cells derived from a transplantable cholangiocarcinoma originally induce d in the liver of a furan-treated rat. An epithelial cell isolate highly en riched in viable cholangiocarcinoma cells was consistently obtained from tr ansplantable cholangiocarcinoma tissue utilizing a similar procedure to tha t recently developed by us to establish a new rt hyperplastic bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro. Primary cholangiocarcinoma cell cultures could be rea dily 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 importa nt characteristic features of the carcinoma cell of th parent tumor, includ ing marked expression of the tyrosine kinase growth factor receptor protein s c-Met nad c-Neu. Under basal culture conditions, the C611B cell line exhi bited a cel doubling time of similar to 24 h and was aneuploid, with a pred ominant chromosomal count of 43. Moreover, C611B cells on collagen gels wer e 100% tumorigenic when transplanted into inguinal fat pads of syngeneic ra ts. All tumors formed at the transplantation site were cytokeratin 19-posit ive, mucin-producing tubular adenocarcinomas whose histological and phenoty pic features closely resembled those of the furan-induced parent transplant able rat cholangiocarcinoma. Based on our findings, we believe that this no vel rat cholangiocarcinoma cell culture model can serve as a valuable resou rce for investigating aberrant growth properties and tumor progression in b iliary cancer.