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

dc.contributor.authorSeitz, Tatjana
dc.contributor.authorFreese, Kim
dc.contributor.authorDietrich, Peter
dc.contributor.authorThasler, Wolfgang Erwin
dc.contributor.authorBosserhoff, Anja
dc.contributor.authorHellerbrand, Claus
dc.date.accessioned2021-01-08
dc.date.available2021-01-01
dc.date.created2020
dc.date.issued2021-01-08
dc.description.abstractHepatocellular 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.en
dc.identifier.citationScientific Reports 10 (2020). <https://www.nature.com/articles/s41598-020-61510-4>
dc.identifier.doihttps://doi.org/10.1038/s41598-020-61510-4
dc.identifier.opus-id15532
dc.identifier.urihttps://open.fau.de/handle/openfau/15532
dc.identifier.urnurn:nbn:de:bvb:29-opus4-155328
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectHepatic stellate cells
dc.subjectHepatocellular carcinoma
dc.subject.ddcDDC Classification::5 Naturwissenschaften und Mathematik :: 57 Biowissenschaften; Biologie :: 572 Biochemie
dc.titleFibroblast Growth Factor 9 is expressed by activated hepatic stellate cells and promotes progression of hepatocellular carcinomaen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleScientific Reports
local.journal.volume10
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2020
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
15532_s41598-020-61510-4.pdf
Size:
3.86 MB
Format:
Adobe Portable Document Format
Description: