TRANSCRIPTIONAL INDUCTION OF THE MELANOCYTE-STIMULATING HORMONE-RECEPTOR IN BRAIN METASTASES OF MURINE K-1735 MELANOMA

Metastatic K-1735 murine melanoma cells are amelanotic in culture or i n the subcutis of syngeneic mice, When injected into the internal caro tid artery, these cells produce melanotic brain metastases, The produc tion of melanin in tumor cells growing in the brain was directly corre lated with induction of melanocyte-stimulating hormone receptor (MSH-R ) steady-state mRNA transcripts. K-1735 cells isolated from brain lesi ons and implanted into the subcutis or grown in culture lose MSH-R tra nscripts and become amelanotic. In contrast to K-1735 cells, B16-BL6 m elanoma cells constitutively produce melanin and express high levels o f MSH-R mRNA regardless of the site of growth. Somatic cell hybrids be tween K-1735 and B16 cells produced melanin and expressed high levels of MSH-R mRNA transcripts, regardless of the site of growth, suggestin g the dominance of the B16 phenotype. Treatment with alpha-MSH failed to upregulate MSH-R expression in cultured K-1735 cells or to maintain MSH-R expression in K-1735 cells isolated from brain metastases to be grown in culture. Responsiveness to alpha-MSH as determined by cell p roliferation, melanin production, and intracellular accumulation of cy clic AMP directly correlated with MSH-R expression. These data demonst rate that a specific organ environment influences the phenotype of met astatic cells by regulation of specific genes that encode for cell sur face receptors.