The influence of extracellular matrix proteins on cutaneous and uveal melanocytes.

Cutaneous and ocular melanocytes are routinely cultured in complex mitogen-rich media. The physiological regulation of melanocyte proliferation and differentiation is not yet fully defined and this study summarises several separate lines of evidence which suggest that, in vivo, some of the signals required for melanocyte proliferation and differentiation may derive from extracellular matrix (ECM) proteins adjacent to these cells. Culture of cutaneous and uveal melanocytes on cell-derived and individual ECM proteins was found to influence cell morphology with such effects being most noticeable in mitogen-deficient media. Similarly, cell-derived and individual ECM proteins increased tyrosinase activity in normal cutaneous melanocytes and effects of these ECM proteins were seen most consistently in mitogen-deficient media. Uveal melanocytes (as has been reported for cutaneous melanocytes) showed preferential attachment to fibronectin over other ECM substrates. This attachment was particularly sensitive to drugs which affected intracellular calcium or calmodulin activity. Acute addition of fibronectin to coverslips of uveal melanocytes loaded with Fura-2 produced an acute and transient increase in intracellular calcium which was more prevalent in 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 intracellular calcium may be part of the signalling system that transmits ECM information into the cell.