Previous studies from our laboratory have suggested that melanomas can be grouped in subsets reflecting stages of melanocyte differentiation. Each of these stages has a characteristic cell surface antigenic phenotype. We have examined the effect of culture of melanoma cell lines representing different stages of differentiation in RPMI medium containing insulin, transferrin, and selenium (ITS). Only cell lines with a phenotype corresponding to early or intermediate stages of melanocyte differentiation could be adapted to culture in ITS medium. ITS cultures showed a decreased reactivity with monoclonal antibodies detecting epidermal growth factor receptor and transferrin receptor. Decreased reactivity with anti-epidermal growth factor receptor antibodies was the result of the production of epidermal growth factor receptor-binding molecules by melanoma cells and down-regulation of the receptor, while decreased cell surface expression of transferrin receptors seemed related to redistribution of receptor molecules to an intracellular pool. Culture of Ia-negative melanomas in ITS medium resulted in expression of major histocompatibility complex Class II antigens. Induction of Ia antigen by culture in ITS medium was constitutive and irreversible. No coordinate changes in phenotypic traits suggestive of induction of differentiation were observed. Melanoma cell lines respond differentially to growth factors, and expression of growth factor receptors and other cell surface molecules is regulated by culture conditions.

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This work was supported by Grants CA-33049 and CA-32152 from the National Cancer Institute, by the Alcoa Foundation, by the Louis and Anne Abrons Foundation, and by the Oliver S. and Jennie R. Donaldson Charitable Trust.

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