Transforming growth factor-alpha induces the differentiation of sarcomatoid cholangiocarcinoma cells.

Abstract

A sarcomatoid cholangiocarcinoma cell line, ETK‐1, was established from a patient. Phenotypically, the cells corresponded to immature biliary epithelial cells. Because a small number of ETK‐1 cells appeared to differentiate spontaneously along a biliary epithelial lineage in continuous culture, we examined the factors that initiate and/or promote the differentiation of the cells. Transforming growth factor‐α (TGFα) induced significant changes in ETK‐1 cells. After stimulation with the factor, ETK‐1 cells displayed morphologic transformation at a much higher frequency, with the appearance of many large cells with intracytoplasmic vacuoles, and the production of mucinous substances. These morphologically transformed cells were phenotypically similar to welldifferentiated adenocarcinoma cells. The expression pattern of integrins after TGFα treatment also supported the maturation of the ETK‐1 cells. The antibody against the receptor of TGFα inhibited these changes by TGFα. Moreover, the proliferation rate of ETK‐1 cells was suppressed by TGFα. Our data suggest that TGFα can act as a differentiation factor along a biliary epithelial lineage.