FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo
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Sara Ghassemi1, Katharina Vejdovszky1, Emine Sahin1, Lukas Ratzinger1, Karin Schelch1, Thomas Mohr1, Barbara Peter-Vörösmarty1, Jelena Brankovic1, Andreas Lackner1, Alexandra Leopoldi1, Diana Meindl1, Christine Pirker1, Balazs Hegedus2,3, Brigitte Marian1, Klaus Holzmann1, Bettina Grasl-Kraupp1, Petra Heffeter1, Walter Berger1 and Michael Grusch1
1Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
2Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
3Department of Thoracic Surgery, Ruhrlandklinik, University Clinic Essen, Unversity of Duisburg-Essen, Duisburg, Germany
Michael Grusch, email: [email protected]
Keywords: FGF5, fibroblast growth factor, melanoma, malignant growth
Received: January 31, 2017 Accepted: August 17, 2017 Published: September 23, 2017
Although FGF5 mRNA was previously found expressed in some melanoma cell lines in contrast to normal human melanocytes, neither its contribution to melanoma growth nor its expression in melanoma tissue has been investigated. Here we demonstrate that ectopic overexpression of FGF5 in human melanoma cells with low endogenous FGF5 expression increased clonogenicity and invasion but not short-term growth in vitro. Silencing of FGF5 in melanoma cells with high endogenous FGF5 expression had the opposite effect on clonogenicity. FGF overexpression led to increased signaling along the MAPK and NFAT axis but had no effect on STAT3 signaling. In an in vivo experiment in immunocompromised mice, human melanoma xenografts overexpressing FGF5 showed enhanced tumor growth, a higher Ki-67 proliferation index, decreased apoptosis and enhanced angiogenesis. Immunohistochemistry performed on a tissue microarray demonstrated FGF5 protein expression in more than 50% of samples of melanoma and benign nevi. These data suggest that FGF5 has oncogenic potential in melanoma cells and contributes to melanoma growth in a subset of patients. This highlights the importance of further evaluating FGF5 as potential biomarker and therapy target in melanoma.
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