Spontaneous and induced differentiation of human melanoma cells

Malignant melanoma cells can differentiate spontaneously in vivo and in vitro into cells with a finite lifespan. Analysis of differentiating cells from primary melanomas in culture revealed a flat, fibroblast-like morphology and expression of the fibroblast-associated marker leucine aminopeptidase (LAP). Differentiation was also observed in a minor sub-population of permanent cell lines derived from metastatic lesions. An experimental model of melanoma cell differentiation was then developed, using the pyrimidine analog bromodeoxyuridine (BUdR). BUdR-treated cells had a flat morphology, were contact-inhibited, had up to 20-fold increased surface area, expressed LAP, no longer proliferated anchorage-independently in soft agar, and 3 out of 4 cell lines were non-tumorigenic in athymic nude mice. Our results show that models of differentiation of melanoma cells can be established that help to define pathways of differentiation.