Hepatocytic phenotypes induced in sarcomatous... : Hepatology (original) (raw)
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Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated with 5-azacytidine
1Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Abstract
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 α-fetoprotein, albumin, integrin α1, and thrombopoietin, but lost such bile duct-specific proteins as integrin α3 and integrin β4. 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.
Copyright © 1997 American Association for the Study of Liver Diseases.