Heparanase, a potential regulator of cell–matrix interactions

Abstract

Dynamic interactions between adherent cells and underlying extracellular matrices are crucial for development, maintenance of cellular functions, and response of tissues to injury and infection. Heparan sulfate proteoglycans are covalently linked protein glycosaminoglycan conjugates found in extracellular matrices and on the surface of most nucleated cells, and play critical roles in cell–cell and cell–matrix interactions (reviewed in 1 Yanagishita M. Hascall V.C. Cell surface heparan sulfate proteoglycans. J. Biol. Chem. 1992; 267: 9451-9454 Abstract Full Text PDF PubMed Google Scholar , 2 Kjellen L. Lindahl U. Proteoglycans: structures and interactions. Annu. Rev. Biochem. 1991; 60: 443-475 Crossref PubMed Scopus (1673) Google Scholar , 3 Bernfield M. et al. Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 1999; 68: 729-777 Crossref PubMed Scopus (2309) Google Scholar ). Most of the biological properties of heparan sulfate proteoglycans are conferred by heparan sulfate, a complex saccharide consisting of alternating hexuronic acid and glucosamine residues modified at various positions by sulfation, epimerization and N-acetylation (see Fig. 1). Heparan sulfate binds to and localizes structural proteins, such as fibronectin and collagen, in the extracellular matrix. Heparan sulfate also tethers chemokines and growth factors to the matrix as high-affinity storage depots of bioactive signaling molecules, whereupon tissue damage triggers rapid localized release of these growth factors to facilitate cellular responses. Cell-associated heparan sulfate can potentiate the interaction of soluble growth factors with their cellular surface receptors, as has been shown for the basic fibroblast growth factor receptor 1 Yanagishita M. Hascall V.C. Cell surface heparan sulfate proteoglycans. J. Biol. Chem. 1992; 267: 9451-9454 Abstract Full Text PDF PubMed Google Scholar , 4 Stringer S.E. Gallagher J.T. Heparan sulphate. Int. J. Biochem. Cell Biol. 1997; 29: 709-714 Crossref PubMed Scopus (123) Google Scholar , 5 Rosenberg R.D. et al. Heparan sulfate proteoglycans of the cardiovascular system. J. Clin. Invest. 1997; 99: 2062-2070 Crossref PubMed Scopus (254) Google Scholar . Binding to heparan sulfate can modulate the activity of the tethered molecule or protect the bound protein from proteolytic cleavage, or both. For example, heparan sulfate regulates the activity of enzymes such as antithrombin III and superoxide dismutase on endothelial cell surfaces to confer anticoagulant and antioxidant properties within blood vessels 4 Stringer S.E. Gallagher J.T. Heparan sulphate. Int. J. Biochem. Cell Biol. 1997; 29: 709-714 Crossref PubMed Scopus (123) Google Scholar , 5 Rosenberg R.D. et al. Heparan sulfate proteoglycans of the cardiovascular system. J. Clin. Invest. 1997; 99: 2062-2070 Crossref PubMed Scopus (254) Google Scholar , 6 Salmivirta M. et al. Heparan sulfate: a piece of information. FASEB J. 1996; 10: 1270-1279 Crossref PubMed Scopus (393) Google Scholar .