Role of growth factors and their receptors in the development and progression of melanoma.

Tumor development and progression is initiated and propelled by the expression of oncogenes and/or inactivation of tumor suppressor genes. Karyotypic alterations in tumor cells lead to malignant properties including uncontrolled proliferation, invasive capability, and metastatic potential. Peptide growth factors and their receptors serve as the major molecular signaling system in orchestrating tumor survival, growth, and interactions with the microenvironment. Aberrant expression of these factors by tumor cells confers growth advantage and competence for metastasis either by autocrine or paracrine mechanisms. In human melanoma, tumor progression is intimately associated with increasing growth autonomy of the malignant cells, perhaps due to the constitutive production of multiple growth factors. Among these, basic fibroblast growth factor (bFGF) is consistently expressed in cultured melanoma cells, but not in normal melanocytes, and it appears to be the main factor produced for autocrine stimulation. In addition, bFGF and other growth factors not apparently involved in autocrine loops are thought to have paracrine roles in tumor development and progression for triggering an inflammatory reaction, initiating angiogenesis and fibrous stroma formation, modulating the host immune response, and activating proteolytic enzymes produced by normal cells. Studies on autocrine and paracrine roles of growth factors in melanoma development and progression will require models that can account for the complex interactions between normal and malignant cells.