Melanoma cell migration is upregulated by tumour necrosis factor-α and suppressed by α-melanocyte-stimulating hormone

Zhu, N., Lalla, R., Eves, Paula , Brown, T.La H., King, A., Kemp, E. H., Haycock, J. W. and MacNeil, S. (2004) Melanoma cell migration is upregulated by tumour necrosis factor-α and suppressed by α-melanocyte-stimulating hormone. British Journal of Cancer, 90 (7). pp. 14573-1463. ISSN 0007-0920

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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. © 2004 Cancer Research UK.

Keywords:Inflammation, Integrin, Melanocortin, Melanoma
Subjects:C Biological Sciences > C130 Cell Biology
C Biological Sciences > C790 Molecular Biology, Biophysics and Biochemistry not elsewhere classified
Divisions:Professional services
ID Code:26991
Deposited On:19 Apr 2017 14:56

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