Stimulation of growth of human melanocytes by tumor promoters

In previous studies we found that, when added to primary normal human epidermal cultures, 12-O-tetradecanoyl phorbol 13-acetate (TPA) (10 ng/ml) selectively suppresses the growth of the otherwise predominant keratinocyte cell population and that this is associated with the outgrowth of normal melanocytes. The present study indicates that these melanocytes can be subsequently grown for at least 30 passages if the medium contains TPA, but if the compound is removed the cells cease to divide. The ability of a series of phorbol esters to support the growth of normal human melanocytes correlates, in general, with their tumor promoting activity on mouse skin. Two structurally unrelated types of compounds which have recently been shown to have tumor promoting activity on mouse skin, teleocidin and aplysiatoxin, also support melanocyte growth. On the other hand, several polypeptide growth factors could not substitute for TPA. Since human melanoma cell lines grow vigorously in the absence of tumor promoters our results suggest that the malignant transformation of melanocytes is associated with the acquisition of autonomy from certain unidentified endogenus growth factors.