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

Eves, Paula and Haycock, J. W. and Layton, C. and Wagner, M. and Kemp, H. and Szabo, M. and Morandini, R. and Ghanem, G. and Garcia-Boron, J. C. and Jiménez-Cervantes, C. and MacNeil, S. (2003) Anti-inflammatory and anti-invasive effects of α-melanocyte- stimulating hormone in human melanoma cells. British Journal of Cancer, 89 (10). pp. 2004-2015. ISSN 0007-0920

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α-Melanocyte stimulating hormone (α-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 α-, β- and γ-MSH correlated clinically with malignant melanoma development, but other studies suggest α-MSH acts to retard invasion. In the present study, we investigated the action of α-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. α-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-κB transcription factor. However, A375-SM and C8161 cells did not respond to α-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 α-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 α-MSH, although all three lines responded to acute α-MSH addition (+ (-)-N6-(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 α-MSH. From this data, we conclude that α-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL). © 2003 Cancer Research UK.

Keywords:?-MSH; Melanocortin; Melanoma; Metastasis; NF-kappaB, ?-melanocyte- stimulating hormone, Melanocortin, Melanoma, metastasis, NF-kappaB
Subjects:B Subjects allied to Medicine > B131 Cellular Pathology
C Biological Sciences > C130 Cell Biology
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:Professional services
ID Code:26992
Deposited On:19 Apr 2017 14:49

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