alpha-Melanocyte stimulating hormone, inflammation and human melanoma

Alpha-melanocyte stimulating hormone (alpha-MSH) arises from the proteolytic cleavage of proopiomelanocortin (POMC) and is the most potent naturally occurring melanotropic peptide. The biological effects of alpha-MSH are mediated via melanocortin receptors (MCRs), which are expressed in virtually every cutaneous cell type. alpha-MSH has pleiotrophic functions including the modulation of a wide range of inflammatory stimuli such as proinflammatory cytokines, adhesion molecules and inflammatory transcription factors. All of the former would be consistent with a cytoprotective role for this hormone in protecting skin cells from exogenous stress, as would occur following UV exposure or exposure to agents inducing inflammation or oxidative stress. In addition to actions on normal skin cells it also modulates both cutaneous and uveal melanoma cell behavior. With respect to melanoma, alpha-MSH is intriguing as studies have shown that while alpha-MSH has the potential to retard metastatic spread (by reducing cell migration and invasion) it is also capable of reducing the ability of the immune system to detect tumor cells (by down regulating adhesion molecules that would normally assist in immune cell interaction with melanoma cells). This review considers the evolving biology of alpha-MSH and discusses its role in man that extend far beyond pigmentation of skin melanocytes, suggesting that the detoxifying role of alpha-MSH in inducing melanogenesis is only one aspect of the stress-coping role of this hormone. Indeed melanoma cells may owe at least some of their success to the 'protective' role of alpha-MSH.