Variable Effects of Retinoids on Two Pigmenting Human Melanoma Cell Lines1

Two melanoma cell lines, each derived from a different patient with metastatic disease, were very similar in their ap pearance, their growth characteristics, and their tendency to differentiate and to pigment in culture as they become con fluent. These lines, UCT-Mel 1 and UCT-Mel 2, were used to study the effects of retinoic acid and other derivatives of vitamin A. When added to UCT-Mel 1 cells, retinoids had only a modest effect on plasminogen activator release and were without mea surable effect on morphology, growth, or tyrosinase synthesis. In contrast, when added to UCT-Mel 2 cells, retinoids ap peared to induce a more differentiated state evident as an inhibition of cell proliferation and the assumption of a dendritic morphology. Paradoxically, however, retinoids caused a strik ing inhibition of the density-dependent intracellular accumula tion of tyrosinase and melanin that was taken to represent spontaneous in vitro differentiation. Culture of UCT-Mel 2 cells in the presence of retinoic acid resulted in initial inhibition followed by marked stimulation of cellular plasminogen activator release. The data suggest that the manner in which retinoids exert their effects on cells in vitro does not depend on the histological origin of the tumor cells being studied but on the innate responsiveness of that partic ular cell line to the retinoid or compound in question.