Collagen-binding domains of gelatinase A and thrombospondin-derived peptides impede endocytic clearance of active gelatinase A and promote HT1080 fibrosarcoma cell invasion

Arnaud Robinet, Hervé Emonard, Laszlo Banyai, Jean Yves Laronze, Lazlo Patthy, William Hornebeck, Georges Bellon

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 KD value of 2 × 10- 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.

Original languageEnglish
Pages (from-to)376-382
Number of pages7
JournalLife sciences
Volume82
Issue number7-8
DOIs
Publication statusPublished - Feb 13 2008

Keywords

  • Cancer invasion
  • Collagen-binding domain
  • Gelatinase A
  • Thrombospondin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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