THE INFLUENCE OF EXTRACELLULAR-MATRIX PROTEINS ON CUTANEOUS AND UVEALMELANOCYTES

Cutaneous and ocular melanocytes are routinely cultured in complex mit ogen-rich media, The physiological regulation of melanocyte proliferat ion and differentiation is not yet fully defined and this study summar ises several separate lines of evidence which suggest that, in vivo, s ome of the signals required for melanocyte proliferation and different iation may derive from extracellular matrix (ECM) proteins adjacent to these cells, Culture of cutaneous and uveal melanocytes on cell-deriv ed and individual ECM proteins was found to influence cell morphology with such effects being most noticeable in mitogen-deficient media. Si milarly, cell-derived and individual ECM proteins increased tyrosinase activity in normal cutaneous melanocytes and effects of these ECM pro teins were seen most consistently in mitogen-deficient media. Uveal me lanocytes (as has been reported for cutaneous melanocytes) showed pref erential attachment to fibronectin over other ECM substrates. This att achment was particularly sensitive to drugs which affected intracellul ar calcium or calmodulin activity Acute addition of fibronectin to cov erslips of uveal melanocytes loaded with Fura-2 produced an acute and transient increase in intracellular calcium which was more prevalent i n low density than higher density cells. We conclude that ECM proteins in vitro are capable of influencing melanocyte morphology, tyrosinase activity and proliferation and that an ECM-induced elevation in intra cellular calcium may be part of the signalling system that transmits E CM information into the cell.