Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated with 5-azacytidine
Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated with 5-azacytidine
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DOI：
10.1002/hep.510260206
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发表时间：
1997-08-01
期刊：
影响因子：
13.5
通讯作者：
Nawata, H
中科院分区：
文献类型：
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作者：
Enjoji, M;Nakashima, M;Nawata, H
在胆管细胞癌(CC)或肝细胞癌(WCC)中发现的肉瘤样细胞尚未得到很好的描述。本研究建立了人肉瘤样癌细胞株ETK-I，观察了分化诱导型S-氮胞苷(5-azaCR)处理前后ETK-1细胞的形态和表型特征。在表型上，ETK-1细胞呈幼稚状态，经5-azaCR诱导形态转化，成功地建立了转化细胞系MEK。MEK细胞表达甲胎蛋白、白蛋白、整合素α(3)和促血小板生成素等肝细胞特异性蛋白，而缺失整合素α(3)和整合素β(4)等胆管特异性蛋白。MEK异种移植瘤的组织病理学与肝细胞癌相似。5-azaCR可使ETK-1细胞转化为肝细胞。另一方面，ETK-1移植瘤被诊断为管状腺癌，肿瘤细胞具有导管表型。这表明ETK-1细胞可以沿着胆管上皮细胞谱系分化。ETK-1和MEK将有助于研究肝细胞分化和胆管上皮细胞向肝细胞系的转化。
The sarcomatoid cells found in cholangiocarcinoma (CC) or hepatocellular carcinoma (WCC) are not well characterized. In this study, a human sarcomatoid CC cell line, ETK-I, 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 S-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 alpha(3) and thrombopoietin, but lost such bile duct-specific protein as integrin alpha(3) and integrin beta(4). 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.