The regulation of cyclic AMP production and the role of cyclic AMP in B16 melanoma cells of differing metastatic potential.

The nature of the relationship between agonist-stimulated cyclic AMP production and metastatic potential was examined in detail for four B16 melanoma cell lines of varying metastatic potential. Highly metastatic cells (B16 F10C1) appeared to differ from cells of low metastatic potential (B16 F1C29) in the degree to which cyclic AMP production in intact cells was stimulated by protein kinase C activation. No significant difference was found in the adenylate-cyclase enzyme activities of the broken cells, irrespective of the agonist used, or in the distribution of cyclic AMP between the intracellular and extracellular compartment. Although B16F1, F10 and F10C1 cells all produced equally pigmented tumors in vivo, the cells differed in their melanogenic response to cyclic AMP elevating agents in vitro: the least metastatic cells produced least agonist-induced cyclic AMP but this induced greatest tyrosinase activation and melanin production in vitro; conversely, the more metastatic cells produced more cyclic AMP but less tyrosinase activation and melanin production in response to agonist stimulation. Thus, agonist-stimulated cyclic AMP production does not appear to be coupled to the differentiated function of melanogenesis for highly metastatic B16 melanoma cells.