ETK-1 Cells

ETK-1 is a human intrahepatic cholangiocarcinoma (IHCCA) cell line originally established from the ascitic fluid of an adult patient with sarcomatoid cholangiocarcinoma. The tumor from which ETK-1 was derived exhibited both tubular adenocarcinoma and sarcomatoid components, and the cell line reflects the sarcomatoid phenotype. ETK-1 cells grow adherently as a uniform epithelial monolayer with a cobblestone appearance, composed mainly of small polygonal cells with round to oval nuclei and prominent nucleoli. Early passage cells demonstrated a population doubling time of approximately 70 hours and a hyperdiploid karyotype with a modal chromosome number in the mid-70s, consistent with chromosomal instability typical of aggressive biliary tract malignancies.

Immunophenotypically, ETK-1 cells express biliary epithelial markers including γ-glutamyl transpeptidase (GGT), cytokeratin 18 (CK18), and cytokeratin 19 (CK19), confirming their cholangiocytic origin. They are negative for hepatocyte-associated markers such as alpha-fetoprotein (AFP) and albumin under basal conditions. ETK-1 cells express vimentin, reflecting their sarcomatoid characteristics and partial mesenchymal phenotype, while lacking expression of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). This marker profile corresponds to the sarcomatoid component observed in the primary tumor and highlights features consistent with epithelial-mesenchymal transition-like properties.

ETK-1 has also been used as a model to study cellular plasticity and lineage differentiation in cholangiocarcinoma. Treatment with the DNA methyltransferase inhibitor 5-azacytidine induced morphological and phenotypic changes, resulting in a derivative cell line with hepatocyte-like features, including expression of AFP, albumin, integrin α1, and thrombopoietin, along with loss of certain biliary markers. In xenograft models, untreated ETK-1 cells form tumors consistent with tubular adenocarcinoma displaying a ductal phenotype. These findings demonstrate that ETK-1 retains differentiation plasticity and serves as a valuable in vitro system for investigating biliary epithelial-to-hepatocytic transdifferentiation, epigenetic regulation, and tumor heterogeneity in intrahepatic cholangiocarcinoma.