Melanoma cell attachment, invasion, and integrin expression is upregulated by tumor necrosis factor α and suppressed by α melanocyte stimulating hormone

Abstract

We have previously shown α-melanocyte stimulating hormone to protect melanocytes and melanoma cells from the proinflammatory actions of tumor necrosis factor-α. The aim of the study was to extend this work to look into the influence of tumor necrosis factor-α on melanoma cell attachment, invasion, and integrin expression and ask to what extent α-melanocyte stimulating hormone might protect cells from tumor necrosis factor-α stimulation of increased integrin expression. HBL human melanoma cells were studied under resting and stressed conditions using tumor necrosis factor-α as a proinflammatory cytokine. Functional information on the actions of tumor necrosis factor-α 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. α3, α4, and β1 integrin expression was detected by Western immunoblotting and the ability of α-melanocyte stimulating hormone to oppose the actions of tumor necrosis factor-α was studied on HBL cell attachment, invasion, and integrin subunit expression. Our results show that tumor necrosis factor-α 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 α3 (28%), α4 (90%), and β1 (65%) integrin subunit expression. In contrast, α-melanocyte stimulating hormone reduced cell attachment, invasion, and integrin expression and opposed the stimulatory effects of tumor necrosis factor-α. In conclusion this study provides further evidence of α-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 α-melanocyte stimulating hormone are consistent with its working in an anti-inflammatory capacity.