title: Melanoma cell attachment, invasion, and integrin expression is upregulated by tumor necrosis factor alpha and suppressed by alpha melanocyte stimulating hormone.
abstract: We have previously shown alpha-melanocyte stimulating hormone to protect melanocytes and melanoma cells from the proinflammatory actions of tumor necrosis factor-alpha. The aim of the study was to extend this work to look into the influence of tumor necrosis factor-alpha on melanoma cell attachment, invasion, and integrin expression and ask to what extent alpha-melanocyte stimulating hormone might protect cells from tumor necrosis factor-alpha stimulation of increased integrin expression. HBL human melanoma cells were studied under resting and stressed conditions using tumor necrosis factor-alpha as a proinflammatory cytokine. Functional information on the actions of tumor necrosis factor-alpha 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. alpha3, alpha4, and beta1 integrin expression was detected by Western immunoblotting and the ability of alpha-melanocyte stimulating hormone to oppose the actions of tumor necrosis factor-alpha was studied on HBL cell attachment, invasion, and integrin subunit expression. Our results show that tumor necrosis factor-alpha 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 alpha3 (28%), alpha4 (90%), and beta1 (65%) integrin subunit expression. In contrast, alpha-melanocyte stimulating hormone reduced cell attachment, invasion, and integrin expression and opposed the stimulatory effects of tumor necrosis factor-alpha. In conclusion this study provides further evidence of alpha-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 alpha-melanocyte stimulating hormone are consistent with its working in an anti-inflammatory capacity.
authors.affiliation: Department of Engineering Materials, Sir Robert Hadfield Building, Sheffield, UK.
authors.forename: Ningwen
authors.initials: N
authors.lastname: Zhu
authors.forename: Paula C
authors.initials: PC
authors.lastname: Eves
authors.forename: Effie
authors.initials: E
authors.lastname: Katerinaki
authors.forename: Marika
authors.initials: M
authors.lastname: Szabo
authors.forename: Renato
authors.initials: R
authors.lastname: Morandini
authors.forename: Ghanem
authors.initials: G
authors.lastname: Ghanem
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
authors.forename: John W
authors.initials: JW
authors.lastname: Haycock
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D039422:Integrin alpha3 / Q000096:biosynthesis; D039441:Integrin alpha4 / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D016023:Integrins / Q000096:biosynthesis*; D008545:Melanoma; D009361:Neoplasm Invasiveness; D016877:Oxidants / Q000494:pharmacology; D012878:Skin Neoplasms; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005353:Fibronectins; D039422:Integrin alpha3; D019012:Integrin beta1; D016023:Integrins; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D039441:Integrin alpha4; D000521:alpha-MSH; D006861:Hydrogen Peroxide