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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 JC, Jiménez-Cervantes C, Mac Neil S - Br. J. Cancer (2003)

Bottom Line: However, A375-SM and C8161 cells did not respond to alpha-MSH.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).

View Article: PubMed Central - PubMed

Affiliation: University Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Sheffield S5 7AU, UK.

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).

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Detection of extracellular (A) and intracellular (B) cAMP in response to increasing concentrations of α-MSH. Symbols: filled circles, mouse melanoma B16F10C1 (positive control); open circles, HBL melanoma cells; filled squares, A375-SM melanoma cells; open squares, C8161 melanoma cells (means±s.e.m., n=3).
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fig3: Detection of extracellular (A) and intracellular (B) cAMP in response to increasing concentrations of α-MSH. Symbols: filled circles, mouse melanoma B16F10C1 (positive control); open circles, HBL melanoma cells; filled squares, A375-SM melanoma cells; open squares, C8161 melanoma cells (means±s.e.m., n=3).

Mentions: The human HBL and murine B16F10-C1 melanoma cell line (used as a positive control) responded to α-MSH concentrations from 10−13 to 10−6 M with increasing cAMP (Figure 3A and BFigure 3


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 JC, Jiménez-Cervantes C, Mac Neil S - Br. J. Cancer (2003)

Detection of extracellular (A) and intracellular (B) cAMP in response to increasing concentrations of α-MSH. Symbols: filled circles, mouse melanoma B16F10C1 (positive control); open circles, HBL melanoma cells; filled squares, A375-SM melanoma cells; open squares, C8161 melanoma cells (means±s.e.m., n=3).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2394449&req=5

fig3: Detection of extracellular (A) and intracellular (B) cAMP in response to increasing concentrations of α-MSH. Symbols: filled circles, mouse melanoma B16F10C1 (positive control); open circles, HBL melanoma cells; filled squares, A375-SM melanoma cells; open squares, C8161 melanoma cells (means±s.e.m., n=3).
Mentions: The human HBL and murine B16F10-C1 melanoma cell line (used as a positive control) responded to α-MSH concentrations from 10−13 to 10−6 M with increasing cAMP (Figure 3A and BFigure 3

Bottom Line: However, A375-SM and C8161 cells did not respond to alpha-MSH.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).

View Article: PubMed Central - PubMed

Affiliation: University Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Sheffield S5 7AU, UK.

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).

Show MeSH
Related in: MedlinePlus