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.