tailieunhanh - Báo cáo khoa học: Proteoglycans in health and disease: new concepts for heparanase function in tumor progression and metastasis

Heparanase is an endo-b-D-glucuronidase capable of cleaving heparan sul-fate side chains at a limited number of sites, yielding heparan sulfate frag-ments of still appreciable size. Importantly, heparanase activity correlates with the metastatic potential of tumor-derived cells, attributed to enhanced cell dissemination as a consequence of heparan sulfate cleavage and remod-eling of the extracellular matrix and basement membrane underlying epithe-lial and endothelial cells. | MINIREVIEW Proteoglycans in health and disease new concepts for heparanase function in tumor progression and metastasis Uri Barash1 Victoria Cohen-Kaplan1 Ilana Dowek2 Ralph D. Sanderson3 Neta Ilan1 and Israel Vlodavsky1 1 Cancer and Vascular Biology Research Center Rappaport Faculty of Medicine Haifa Israel 2 Department of Otolaryngology Head and Neck Surgery CarmelMedicalCenter Haifa Israel 3 Department of Pathology University of Alabama at Birmingham Birmingham AL USA Keywords C-domain EGFR head and neck carcinoma heparanase heparan sulfate lymph angiogenesis MMP myeloma signaling splice variant Correspondence I. Vlodavsky Cancer and Vascular Research Center Rappaport Faculty of Medicine Technion P. O. Box 9649 Haifa 31096 Israel Fax 972 4 8510445 Tel 972 4 8295410 E-mail vlodavsk@ Received 7 April2010 revised 29 June 2010 accepted 1 July 2010 doi Heparanase is an endo-b-D-glucuronidase capable of cleaving heparan sulfate side chains at a limited number of sites yielding heparan sulfate fragments of still appreciable size. Importantly heparanase activity correlates with the metastatic potential of tumor-derived cells attributed to enhanced cell dissemination as a consequence of heparan sulfate cleavage and remodeling of the extracellular matrix and basement membrane underlying epithelial and endothelial cells. Similarly heparanase activity is implicated in neovascularization inflammation and autoimmunity involving the migration of vascular endothelial cells and activated cells of the immune system. The cloning of a single human heparanase cDNA 10 years ago enabled researchers to critically approve the notion that heparan sulfate cleavage by heparanase is required for structural remodeling of the extracellular matrix thereby facilitating cell invasion. Progress in the field has expanded the scope of heparanase function and its significance in tumor progression and other pathologies. Notably although heparanase .