Fibroblast Growth Factor 19 Induced Changes in Non-malignant Cholangiocytes

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Background and Aims: Fibroblast growth factor (FGF)19 has been implicated in the pathogenesis of murine hepa-tocellular carcinoma. Whether it plays a role in the devel-opment or course of human cholangiocarcinoma remains to be determined. The aim of this study was to determine whether prolonged exposure to FGF19 results in the trans-formation of non-malignant human cholangiocytes into cells with malignant features. Methods: Human SV-40 trans-fected non-malignant H69 cholangiocytes were cultured with FGF19 (0-50 ng/mL) for 6 weeks, followed by 6 weeks with medium alone. Cell proliferation, invasion, stem cell surface markers, oncofetoprotein expression, state of dif-ferentiation, epithelial-mesenchymal transition (EMT) and interleukin (IL)-6 expression were documented at various time intervals throughout the 12-week period. Results: FGF19 exposure was associated with significant increases in cell proliferation, de-differentiation, EMT and IL-6 expres-sion. However, each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period. The remaining cell properties remained unaltered. Conclusions: Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant, human cholangiocytes.
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