1. ^*Department of Engineering Materials, Sir Robert Hadfield Building, Sheffield, U.K.
2. ^†Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Sheffield, U.K.
3. ^‡Laboratory of Oncology and Experimental Surgery, Institut Bordet, Université Libre de Bruxelles, Belgium
4. ^§Academic Department of Clinical Oncology, Weston Park Hospital, Sheffield, U.K.

Correspondence: Dr John Haycock, Department of Engineering Materials, Sir Robert Hadfield Building, Mappin Street, Sheffield, S1 3JD, U.K.; Email: j.w.haycock@sheffield.ac.uk

Received 4 June 2002; Revised 31 July 2002; Accepted 5 August 2002.

Abstract

We have previously shown -melanocyte stimulating hormone to protect melanocytes and melanoma cells from the proinflammatory actions of tumor necrosis factor-. The aim of the study was to extend this work to look into the influence of tumor necrosis factor- on melanoma cell attachment, invasion, and integrin expression and ask to what extent -melanocyte stimulating hormone might protect cells from tumor necrosis factor- stimulation of increased integrin expression. HBL human melanoma cells were studied under resting and stressed conditions using tumor necrosis factor- as a proinflammatory cytokine. Functional information on the actions of tumor necrosis factor- on melanoma cells was obtained by examining the strength of attachment of melanoma cells to substrates and the ability of melanoma cells to invade through fibronectin. 3, 4, and 1 integrin expression was detected by Western immunoblotting and the ability of -melanocyte stimulating hormone to oppose the actions of tumor necrosis factor- was studied on HBL cell attachment, invasion, and integrin subunit expression. Our results show that tumor necrosis factor- increases the number of melanoma cells attaching to collagen (types I and IV) and tissue culture polystyrene, increases ability to invade through fibronectin, and upregulates the expression of 3 (28%), 4 (90%), and 1 (65%) integrin subunit expression. In contrast, -melanocyte stimulating hormone reduced cell attachment, invasion, and integrin expression and opposed the stimulatory effects of tumor necrosis factor-. In conclusion this study provides further evidence of -melanocyte stimulating hormone acting to "protect" melanoma cells from proinflammatory cytokine action. Our data support a hypothesis that an inflammatory environment would promote melanoma invasion and that the anti-invasive actions of -melanocyte stimulating hormone are consistent with its working in an anti-inflammatory capacity.