Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.

Détails

ID Serval
serval:BIB_9B2394D27922
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.
Périodique
Genes and Development
Auteur(s)
Yu Q., Stamenkovic I.
ISSN
0890-9369[print], 0890-9369[linking]
Statut éditorial
Publié
Date de publication
2000
Volume
14
Numéro
2
Pages
163-176
Langue
anglais
Résumé
We have uncovered a novel functional relationship between the hyaluronan receptor CD44, the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-beta in the control of tumor-associated tissue remodeling. CD44 provides a cell surface docking receptor for proteolytically active MMP-9 and we show here that localization of MMP-9 to cell surface is required for its ability to promote tumor invasion and angiogenesis. Our observations also indicate that MMP-9, as well as MMP-2, proteolytically cleaves latent TGF-beta, providing a novel and potentially important mechanism for TGF-beta activation. In addition, we show that MMP-9 localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-beta. These observations suggest that coordinated CD44, MMP-9, and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion.
Mots-clé
Animals, Antigens, CD44/physiology, Cell Membrane/enzymology, Culture Media, Conditioned/pharmacology, Endothelium, Vascular/enzymology, Endothelium, Vascular/pathology, Hydrolysis, Keratinocytes/enzymology, Keratinocytes/metabolism, Male, Mammary Neoplasms, Experimental/blood supply, Mammary Neoplasms, Experimental/enzymology, Matrix Metalloproteinase 9/metabolism, Mice, Mice, Inbred A, Mice, Mutant Strains, Neoplasm Invasiveness, Neovascularization, Pathologic/enzymology, Neovascularization, Pathologic/metabolism, Peptide Hydrolases/metabolism, Protein Isoforms/metabolism, Transforming Growth Factor beta/metabolism, Tumor Cells, Cultured
Pubmed
Création de la notice
26/08/2010 17:40
Dernière modification de la notice
20/08/2019 16:02
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