Metastatic K-1735 murine
melanoma cells are amelanotic in culture or in the subcutis of syngeneic mice. When injected into the internal carotid artery, these cells produce melanotic
brain metastases. The production of
melanin in
tumor cells growing in the brain was directly correlated with induction of
melanocyte-stimulating hormone receptor (
MSH-R) steady-state
mRNA transcripts. K-1735 cells isolated from brain lesions and implanted into the subcutis or grown in culture lose
MSH-R transcripts and become amelanotic. In contrast to K-1735 cells, B16-BL6
melanoma cells constitutively produce
melanin and express high levels of
MSH-R
mRNA regardless of the site of growth. Somatic cell hybrids between K-1735 and B16 cells produced
melanin and expressed high levels of
MSH-R
mRNA transcripts, regardless of the site of growth, suggesting 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 proliferation,
melanin production, and intracellular accumulation of
cyclic AMP directly correlated with
MSH-R expression. These data demonstrate that a specific organ environment influences the phenotype of metastatic cells by regulation of specific genes that encode for
cell surface receptors.