title: Copper-mediated cross-linking of S100A4, but not of S100A2, results in proinflammatory effects in melanoma cells.
abstract: The aim of this study was to investigate the response to and the physiological consequences of copper-mediated cross-linking of S100A2 and S100A4, two members of the S100 family of EF-hand calcium-binding proteins. As demonstrated by electrophoresis and mass spectrometry techniques S100A2 and S100A4 show formation of cross-links due to copper-mediated oxidation of cysteine residues. For S100A4, but not for S100A2, this results in both increased activation of NFκB and secretion of TNF-α in human A375 and, to a higher extent, in RAGE-transfected melanoma cells. The data suggest that a prooxidative tumor microenvironment enhances proinflammatory and prometastatic action of S100A4.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmacy, Department of Radiopharmaceutical Biology, Dresden, Germany. c.haase@hzdr.de
authors.forename: Cathleen
authors.initials: C
authors.lastname: Haase-Kohn
authors.forename: Susann
authors.initials: S
authors.lastname: Wolf
authors.forename: Jens
authors.initials: J
authors.lastname: Lenk
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002630:Chemotactic Factors / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism*; D059016:Tumor Microenvironment; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002630:Chemotactic Factors; D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C098997:S100A2 protein, human; D014409:Tumor Necrosis Factor-alpha; C077591:S100A4 protein, human; D003300:Copper; D003545:Cysteine