Eves, P., Haycock, J. orcid.org/0000-0002-3950-3583, Layton, C. et al. (8 more authors) (2003) Anti-inflammatory and anti-invasive effects of alpha-melanocyte-stimulating hormone in human melanoma cells. British Journal of Cancer, 89 (10). pp. 2004-2015. ISSN 0007-0920
Abstract
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).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2003 Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
Keywords: | melanoma; alpha-MSH; melanocortin; NF-kappaB; metastasis; cultured human melanocytes;necrosis-factor-alpha; murine B16 melanoma;reconstructed human skin; NF-KAPPA-B; MSH receptors; malignant-melanoma; in-vitro; melanocortin-1 receptor; human keratinocytes |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Jul 2016 13:57 |
Last Modified: | 28 Jul 2016 14:04 |
Published Version: | http://dx.doi.org/10.1038/sj.bjc.6601349 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1038/sj.bjc.6601349 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:81468 |
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Licence: CC-BY-NC-SA 3.0