Zhu, N., Lalla, R., Eves, P. et al. (5 more authors) (2004) Melanoma cell migration is upregulated by tumour necrosis factor-alpha and suppressed by alpha-melanocyte-stimulating hormone. British Journal of Cancer, 90 (7). 1457 - 1463. ISSN 0007-0920
Abstract
We reported recently that the inflammatory cytokine tumour necrosis factor α (TNF-α) can upregulate integrin expression, cell attachment and invasion of cells through fibronectin in a human melanoma cell line (HBL). Furthermore, the actions of TNF-α were suppressed by the addition of an anti-inflammatory peptide α-melanocyte-stimulating hormone (α-MSH). In the current study, we extend this work investigating to what extent TNF-α might stimulate melanoma invasion by promoting cell migration and whether α-MSH is also inhibitory. Two human melanoma cell lines were examined in vitro (HBL and C8161) using a scratch migration assay. Analysis using either time-lapse video microscopy or imaging software analysis of migrating ‘fronts’ of cells revealed that C8161 cells migrated more rapidly than HBL cells. However, when cells were stimulated with TNF-α both cell types responded with a significant increase in migration distance over a 16–26 h incubation time. α-Melanocyte-stimulating hormone had an inhibitory effect on TNF-α-stimulated migration for HBL cells, completely blocking migration at 10−9 m. In contrast, C8161 cells did not respond to α-MSH (as these cells have a loss-of-function melanocortin-1 receptor). However, stable transfection of C8161 cells with the wild-type melanocortin-1 receptor produced cells whose migration was significantly inhibited by α-MSH. In addition, the use of a neutralising antibody to the β1-integrin subunit significantly reduced migration in both cell types. This data therefore supports an inflammatory environment promoting melanoma cell migration, and in addition shows that α-MSH can inhibit inflammatory stimulated migration. The data also support a fundamental role of the β1-integrin receptor in melanoma cell migration.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2004 The Author(s). 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; inflammation; integrin; melanocortin; IN-VITRO; INTEGRIN EXPRESSION; ADHESION MOLECULES; MALIGNANT-MELANOMA; CANCER CELLS; TNF-ALPHA; KAPPA-B; MODULATION; INVASION; LINES |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Jun 2015 10:01 |
Last Modified: | 03 Nov 2016 01:47 |
Published Version: | http://dx.doi.org/10.1038/sj.bjc.6601698 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/sj.bjc.6601698 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:81469 |