Anti-inflammatory and anti-invasive effects of alpha-melanocyte-stimulating hormone in human melanoma cells.

Abstract

Alpha-melanocyte stimulating hormone (alpha-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of alpha-, beta- and gamma-MSH correlated clinically with malignant melanoma development, but other studies suggest alpha-MSH acts to retard invasion. In the present study, we investigated the action of alpha-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. alpha-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kappaB transcription factor. However, A375-SM and C8161 cells did not respond to alpha-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for alpha-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to alpha-MSH, although all three lines responded to acute alpha-MSH addition (+(-)-N(6)-(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by alpha-MSH. From this data, we conclude that alpha-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).

• Authors: P Eves, J Haycock, C Layton, M Wagner, H Kemp, M Szabo, R Morandini, G Ghanem, J C García-Borrón, C Jiménez-Cervantes, S Mac Neil
• Journal: British journal of cancer (Br J Cancer) Vol. 89 Issue 10 Pg. 2004-15 (Nov 17 2003) ISSN: 0007-0920 [Print] England
• PMID: 14612916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• alpha-MSH

Topics

• Cytokines (pharmacology)
• Humans
• Inflammation
• Keratinocytes
• Melanoma (pathology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Skin Neoplasms (pathology)
• Tumor Cells, Cultured
• alpha-MSH (pharmacology)