title: Collagen-binding domains of gelatinase A and thrombospondin-derived peptides impede endocytic clearance of active gelatinase A and promote HT1080 fibrosarcoma cell invasion.
abstract: Gelatinase A (matrix metalloproteinase-2, MMP-2) binds to several proteins through its collagen-binding domains (CBDs). Surface plasmon resonance analysis revealed a strong interaction between CBD123 and thrombospondin-1 (TSP-1), with a K(D) value of 2x10(-9) M. CBD123, as well as individual domains, behave as competitive inhibitors of the TSP-1-directed endocytic clearance of active MMP-2, but not of its latent form, by HT1080 fibrosarcoma cells. Enhanced level of active MMP-2 in conditioned medium was associated to increased matrigel invasion. Similarly, GGWSHWSPWSS and GGWSHW peptides, as tryptophan-rich peptides within properdin-repeat motifs (TSRs) of TSP-1, promoted MMP-2 accumulation and cell invasiveness. Our data document the importance of TSP-1 in promoting MMP-2-mediated cancer cell invasion through interaction between CBDs of the enzyme and TSRs motifs of TSP-1.
authors.affiliation: University of Reims Champagne-Ardenne, Faculty of Medecine, UMR 6237 CNRS, Reims, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Robinet
authors.forename: Hervé
authors.initials: H
authors.lastname: Emonard
authors.forename: Laszlo
authors.initials: L
authors.lastname: Banyai
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Laronze
authors.forename: Lazlo
authors.initials: L
authors.lastname: Patthy
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
authors.forename: Georges
authors.initials: G
authors.lastname: Bellon
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005347:Fibroblasts; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D019700:Thrombospondin 1 / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D019700:Thrombospondin 1; D003094:Collagen; D020778:Matrix Metalloproteinase 2