Differential expression of melanoma-associated growth factors in keratinocytes and fibroblasts by ultraviolet A and ultraviolet B radiation

Abstract

Besides the direct DNA-damaging effects of ultraviolet (UV) radiation on cells, indirect effects on the microenvironment of the skin may facilitate melanoma development. A stimulation of growth factor production by cells in the immediate environment of melanocytes may lead to a paracrine activation and proliferation of melanocytes that in turn become more susceptible to transformation. We investigated whether the expression of growth factors for melanocytes can be modulated in keratinocytes and fibroblasts by UVA or UVB. After irradiation with different doses of UVA or UVB, protein expression of basic fibroblast growth factor (bFGF), endothelin (ET)-1, transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AA, stem cell factor (SCF) and hepatocyte growth factor (HGF) was analysed by quantitative enzyme-linked immunosorbent assay. The mRNA expression of bFGF and ET-1 was analysed by quantitative real-time reverse transcriptase-polymerase chain reaction. In keratinocytes, UVB and UVA increased bFGF protein levels up to 2.6-fold. This increase was paralleled by elevated mRNA levels. UVB also induced ET-1 protein up to 1.8-fold, while UVA led to an 80% decrease. Secreted TGF-beta1 and PDGF-AA were downregulated by UVA by less than 50%, while there was no significant alteration by UVB. Secreted SCF was not changed significantly by UVA or UVB. In fibroblasts, bFGF protein levels were increased 11-64-fold by UVA and 34-61-fold by UVB. This was paralleled by elevated mRNA levels for bFGF up to 2.7-fold. HGF protein was stimulated by UVA up to 2.8-fold and by UVB up to 6.7-fold, while TGF-beta1 protein was increased up to 2.7-fold by UVB and 1.7-fold by UVA. UVA and UVB can stimulate and inhibit the production of growth factors for melanocytes in keratinocytes and fibroblasts dependent on the cell type and wavelength. We show for the first time that UVA and UVB can activate bFGF, HGF and TGF-beta1 in fibroblasts, while bFGF was the most inducible factor both in fibroblasts and in keratinocytes. The induction of bFGF and HGF in fibroblasts by UVA suggests that stroma cells in the dermis may be involved in the UV activation of melanocytes via paracrine ways and thus promote melanoma development.