FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo

// Sara Ghassemi 1 , Katharina Vejdovszky 1 , Emine Sahin 1 , Lukas Ratzinger 1 , Karin Schelch 1 , Thomas Mohr 1 , Barbara Peter-Vorosmarty 1 , Jelena Brankovic 1 , Andreas Lackner 1 , Alexandra Leopoldi 1 , Diana Meindl 1 , Christine Pirker 1 , Balazs Hegedus 2, 3 , Brigitte Marian 1 , Klaus Holzmann 1 , Bettina Grasl-Kraupp 1 , Petra Heffeter 1 , Walter Berger 1 and Michael Grusch 1 1 Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria 2 Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria 3 Department of Thoracic Surgery, Ruhrlandklinik, University Clinic Essen, Unversity of Duisburg-Essen, Duisburg, Germany Correspondence to: Michael Grusch, email: michael.grusch@meduniwien.ac.at Keywords: FGF5, fibroblast growth factor, melanoma, malignant growth Received: January 31, 2017     Accepted: August 17, 2017     Published: September 23, 2017 ABSTRACT 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.