title: TNF-alpha increases human melanoma cell invasion and migration in vitro: the role of proteolytic enzymes.
abstract: Inflammatory mediators have been reported to promote malignant cell growth, invasion and metastatic potential. More specifically, we have recently reported that tumour necrosis factor alpha (TNF-alpha) increases melanoma cell attachment to extracellular matrix (ECM) substrates and invasion through fibronectin. In this study, we extend these investigations asking specifically whether the TNF-alpha effect on cell invasion and migration involves activation of proteolytic enzymes. We examined the effect of TNF-alpha on melanoma expression/activation of type IV gelatinases matrix metalloproteinases 2 and 9 (MMPs -2 and -9) and general proteolytic enzymes. Stimulation with TNF-alpha significantly increased both melanoma cell migration at 24 h (+21%) and invasion through fibronectin (+35%) but did not upregulate/activate the expression of latent MMP-2 constitutively produced by these cells and did not upregulate their general protease activity. However, the increased cell migration and invasion through fibronectin observed following stimulation with TNF-alpha were inhibited by the general protease inhibitor alpha(2) macroglobulin. These findings suggest that the promigratory and proinvasive effect of TNF-alpha on this melanoma cell line may be mediated to some extent by induction of localised cell membrane-bound degradative enzyme activity, which is not readily detected in biochemical assays.
authors.affiliation: Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
authors.forename: E
authors.initials: E
authors.lastname: Katerinaki
authors.forename: G S
authors.initials: GS
authors.lastname: Evans
authors.forename: P C
authors.initials: PC
authors.lastname: Lorigan
authors.forename: S
authors.initials: S
authors.lastname: MacNeil
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects*; D004789:Enzyme Activation; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010447:Peptide Hydrolases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005353:Fibronectins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D010447:Peptide Hydrolases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9