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Anti-inflammatory and anti-invasive effects of alpha-melanocyte-stimulating hormone in human melanoma cells.
Eves, P; Haycock, J; Layton, C; Wagner, M; Kemp, H; Szabo, M; Morandini, R; Ghanem, G; García-Borrón, J C; Jiménez-Cervantes, C; Mac Neil, S.
Afiliação
  • Eves P; University Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Sheffield S5 7AU, UK.
Br J Cancer ; 89(10): 2004-15, 2003 Nov 17.
Article em En | MEDLINE | ID: mdl-14612916
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).
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Alfa-MSH / Melanoma / Invasividade Neoplásica Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Alfa-MSH / Melanoma / Invasividade Neoplásica Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article