Tumor progression in melanoma: the biology of epidermal melanocytes in vitro

The propagation of pigmented cells derived from normal skin, common and precursor nevi, and primary and metastatic melanoma in tissue culture has allowed the study of tumor progression under experimental conditions. In accordance with Clark's hypothesis, which is based on histopathological observations, cells isolated from different stages of tumor progression show a stepwise development of a malignant phenotype as defined by different biological parameters: life span in culture, anchorage-independent growth, increased growth autonomy from exogenous growth factors, expression of melanoma-associated antigens, progressively severe chromosomal abnormalities, and tumorigenicity in nude mice. Qualitative and quantitative differences exist between normal melanocytes and nevus cells on the one hand, and between VGP primary and metastatic melanoma cells on the other. Little information, however, is available on cells from dysplastic nevi and RGP primary melanoma cells. Preliminary results suggest that the biologic, immunologic and genetic characterization of these cells from the intermediate stages of tumor development will significantly increase our understanding of the pathogenesis of melanoma.