In CRH positive melanomas, seven out of nine cases (78%) of primary melanoma, and 7 out of 12 cases (58%) of MetM showed colocalization of CRH and POMC peptides.
However, melanoma cells synthesize and release alpha-melanocyte stimulating hormone (alphaMSH, the ligand for MC1R), therefore MC1R variants could alter the autocrine effects of alphaMSH on melanoma cell behaviour, thereby affecting early melanoma development and progression via non-pigmentary mechanisms.
Alpha-MSH, a proopiomelanocortin (POMC)-derived peptide, is known to be produced in the pituitary, the skin, and melanoma tumors and to possess many biological effects, mainly on melanocyte pigmentation and growth.
The human melanocortin-1 (MC1) receptor was stably expressed in the amelanotic mouse melanoma cell clone B16-G4F which does not express its own (mouse) MC1 receptor and hence is unresponsive to alpha melanocyte stimulating hormone (alpha MSH).
In contrast to melanoma cells, nevus cells in serum-free medium require the presence of alpha-melanocyte-stimulating hormone, which enhanced intracellular levels of cyclic adenosine monophosphate.