Collagen-binding domains of gelatinase A and thrombospondin-derived peptides impede endocytic clearance of active gelatinase A and promote HT1080 fibrosarcoma cell invasion.
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.
Robinet
Arnaud
A
University of Reims Champagne-Ardenne, Faculty of Medecine, UMR 6237 CNRS, Reims, France.
Emonard
Hervé
H
Banyai
Laszlo
L
Laronze
Jean-Yves
JY
Patthy
Lazlo
L
Hornebeck
William
W
Bellon
Georges
G
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*
D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D019700:Thrombospondin 1; D003094:Collagen; D020778:Matrix Metalloproteinase 2