Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated with 5-azacytidine.
The sarcomatoid cells found in cholangiocarcinoma (CC) or hepatocellular carcinoma (HCC) are not well characterized. In this study, a human sarcomatoid CC cell line, ETK-1, was established from a patient, and then morphological and phenotypical characteristics of the ETK-1 cells were evaluated before and after treatment with differentiation-inducing 5-azacytidine (5-azaCR). Phenotypically, the ETK-1 cells appeared immature. Exposure to 5-azaCR induced morphological transformation; a converted cell line, MEK, was successfully established. The MEK cells expressed such hepatocyte-specific proteins as alpha-fetoprotein, albumin, integrin alpha1, and thrombopoietin, but lost such bile duct-specific proteins as integrin alpha3 and integrin beta4. The histopathology of MEK xenografts resembled that of HCC. The ETK-1 cells appeared to be converted into hepatocytes by exposure to 5-azaCR. On the other hand, ETK-1 xenografts were diagnosed as tubular adenocarcinoma, and the tumor cells had a ductal phenotype. This suggests the possibility that ETK-1 cells can differentiate along a biliary epithelial cell lineage. ETK-1 and MEK will be useful in studying hepatocytic differentiation and the transformation from a biliary epithelial cell to a hepatocytic lineage.
Enjoji
M
M
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nakashima
M
M
Honda
M
M
Sakai
H
H
Nawata
H
H
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D001650:Bile Duct Neoplasms / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D002454:Cell Differentiation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D010641:Phenotype; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis
D000964:Antimetabolites, Antineoplastic; D014746:Vimentin; D001374:Azacitidine