Fibroblast Growth Factor 9 is expressed by activated hepatic stellate cells and promotes progression of hepatocellular carcinoma

Seitz T, Freese K, Dietrich P, Thasler WE, Boßerhoff AK, Hellerbrand C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 10

Article Number: 4546

Journal Issue: 1

DOI: 10.1038/s41598-020-61510-4

Abstract

Hepatocellular carcinoma (HCC) is closely associated with liver fibrosis. Hepatic stellate cells (HSC) and cancer-associated myofibroblasts are key players in liver fibrogenesis and hepatocarcinogenesis. Overexpression of fibroblast growth factor (FGF) receptors contributes to HCC development and progression. This study aimed to elucidate the role of FGFs in the HSC-HCC crosstalk. Analysis of the expression of the fifteen paracrine FGF-members revealed that FGF9 was only expressed by HSC but not by HCC cells. Also in human HCC tissues, HSC/stromal myofibroblasts were identified as cellular source of FGF9. High expression levels of FGF9 significantly correlated with poor patient survival. Stimulation with recombinant FGF9 induced ERK- and JNK-activation combined with significantly enhanced proliferation, clonogenicity, and migration of HCC cells. Moreover, FGF9 significantly reduced the sensitivity of HCC cells against sorafenib. Protumorigenic effects of FGF9 on HCC cells were almost completely abrogated by the FGFR1/2/3 inhibitor BGJ398, while the selective FGFR4 inhibitor BLU9931 had no significant effect. In conclusion, these data indicate that stroma-derived FGF9 promotes tumorigenicity and sorafenib resistance of HCC cells and FGF9 overexpression correlates with poor prognosis in HCC patients. Herewith, FGF9 appears as potential prognostic marker and novel therapeutic target in HCC.

Authors with CRIS profile

Tatjana Seitz Professur für Biochemie und Molekulare Pathobiologie Kim Freese Lehrstuhl für Biochemie und Molekulare Medizin Peter Dietrich Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

D032: The role of neuropeptide Y in chemo-resistance and immune checkpoint inhibition in hepatocellular carcinoma March 1, 2020 - Feb. 28, 2023

Involved external institutions

Hepacult GmbH DE Germany (DE)

How to cite

APA:

Seitz, T., Freese, K., Dietrich, P., Thasler, W.E., Boßerhoff, A.K., & Hellerbrand, C. (2020). Fibroblast Growth Factor 9 is expressed by activated hepatic stellate cells and promotes progression of hepatocellular carcinoma. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-61510-4

MLA:

Seitz, Tatjana, et al. "Fibroblast Growth Factor 9 is expressed by activated hepatic stellate cells and promotes progression of hepatocellular carcinoma." Scientific Reports 10.1 (2020).

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