Autocrine and Paracrine Roles for Growth Factors in Melanoma.

Distinct biologic and histopathological features characterizing each stage of tumor progression toward a more aggressive phenotype have been defined in the human melanocytic cell system. One of the most significant aspects accompanying melanoma progression is the acquisition of growth autonomy and the expression of multiple growth factors and receptors by tumor cells but not by normal melanocytes. Among the growth factors produced by melanoma cells, bFGF, TGF-alpha, TGF-beta, PDGF A and B chains, MGSA, and interleukins have been extensively characterized. The complex signaling networks mediated by these melanoma-derived factors are responsible for the autocrine growth stimulation of melanoma cells and for paracrine actions of growth factors in the generation of a microenvironment favorable for tumor survival and invasion. bFGF is the best characterized candidate for autocrine stimulation in melanoma cells. In addition, bFGF and other growth factors not apparently involved in autocrine loops have been shown to activate neighboring stromal cells and to participate in angiogenesis, fibrous stroma formation, activation of proteolytic enzymes produced by normal cells, promotion of adhesive interactions between tumor cells and extracellular matrix and endothelium, and suppression of local immunity. Experimental models that can account for the complex interactions between normal and tumor cells are needed to further explore the roles of autocrine and paracrine actions of growth factors and their receptors in melanoma development and progression.