Transforming growth factor-alpha induces the differentiation of sarcomatoid cholangiocarcinoma cells.
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-alpha (TGFalpha) 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 well-differentiated adenocarcinoma cells. The expression pattern of integrins after TGFalpha treatment also supported the maturation of the ETK-1 cells. The antibody against the receptor of TGFalpha inhibited these changes by TGFalpha. Moreover, the proliferation rate of ETK-1 cells was suppressed by TGFalpha. Our data suggest that TGFalpha can act as a differentiation factor along a biliary epithelial lineage.
Enjoji
M
M
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka. enjoji@intmed3.med.kyushu-u.ac.jp
Nakashima
M
M
Nakamuta
M
M
Nawata
H
H
D001650:Bile Duct Neoplasms / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D002454:Cell Differentiation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000473:pathology*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016023:Integrins; D017468:Receptors, Fibroblast Growth Factor; D016211:Transforming Growth Factor alpha; D016220:Fibroblast Growth Factor 1; D019009:Proto-Oncogene Proteins c-kit