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    Sodium salicylate inhibits TNF-alpha-induced NF-kappaB activation, cell migration, invasion and ICAM-1 expression in human melanoma cells.

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    Authors
    Katerinaki, Efthymia
    Haycock, John W
    Lalla, Ravindra
    Carlson, Kenneth E
    Yang, Yifan
    Hill, Rebecca P
    Lorigan, Paul C
    MacNeil, Sheila
    Affiliation
    University of Sheffield, Section of Human Metabolism, Division of Clinical Sciences, Northern General Hospital, Sheffield, UK.
    Issue Date
    2006-02
    
    Metadata
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    Abstract
    We have previously shown that tumour necrosis factor-alpha (TNF-alpha) upregulates human melanoma cell integrin expression, migration and invasion in vitro. The aim of this study was to investigate the effect of the non-steroidal anti-inflammatory agent sodium salicylate on TNF-alpha-induced activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and upregulation of intercellular adhesion molecule-1 (ICAM-1), and TNF-alpha-stimulated cell migration and invasion through fibronectin. HBL human melanoma cells were pre-incubated with sodium salicylate prior to stimulation with TNF-alpha for 24 h. NF-kappaB activation was measured using an assay that detects changes in the expression of a luciferase reporter gene under the direct control of NF-kappaB transcriptional activity. The effect of sodium salicylate and TNF-alpha on HBL cell invasion over 20 h and migration over 24 h was studied using fibronectin invasion and 'scratch wound' migration models in vitro, as described previously. Sodium salicylate inhibited TNF-alpha-stimulated NF-kappaB activation in melanoma cells in a concentration-dependent manner, and this was achieved with pre-incubation times as short as 15 min. TNF-alpha-stimulated ICAM-1 expression in HBL cells was also downregulated by sodium salicylate, although in a manner inversely related to the concentration of this agent. In functional assays, TNF-alpha stimulated migration and invasion, and sodium salicylate significantly reduced the extent of melanoma invasion and migration in both the presence and absence of TNF-alpha. In conclusion, sodium salicylate effectively inhibited TNF-alpha-induced upregulation of NF-kappaB, ICAM-1 expression, in-vitro migration and invasion in human melanoma cells, indicating that non-steroidal anti-inflammatory drugs may be a useful therapeutic approach to oppose inflammation-induced melanoma invasion and metastasis in vivo.
    Citation
    Sodium salicylate inhibits TNF-alpha-induced NF-kappaB activation, cell migration, invasion and ICAM-1 expression in human melanoma cells. 2006, 16 (1):11-22 Melanoma Res.
    Journal
    Melanoma Research
    URI
    http://hdl.handle.net/10541/72692
    DOI
    10.1097/01.cmr.0000195698.58013.53
    PubMed ID
    16432451
    Type
    Article
    Language
    en
    ISSN
    0960-8931
    ae974a485f413a2113503eed53cd6c53
    10.1097/01.cmr.0000195698.58013.53
    Scopus Count
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    All Paterson Institute for Cancer Research

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