title: The heparanase system and tumor metastasis: is heparanase the seed and soil?
abstract: Tumor metastasis, the leading cause of cancer patients' death, is still insufficiently understood. While concepts and mechanisms of tumor metastasis are evolving, it is widely accepted that cancer metastasis is accompanied by orchestrated proteolytic activity executed by array of proteases. While matrix metalloproteinases (MMPs) attracted much attention, other proteases constitute the tumor milieu, of which a large family consists of cysteine proteases named cathepsins. Like MMPs, some cathepsins are often upregulated in cancer and, once secreted or localized to the cell surface, can degrade components of the extracellular matrix. In addition, cathepsin L is held responsible for processing and activation of heparanase, an endo-β-glucuronidase capable of cleaving heparan sulfate side chains of heparan sulfate proteoglycans, activity that is strongly implicated in cell dissemination associated with tumor metastasis, angiogenesis, and inflammation. In this review, we discuss recent progress in heparanase research focusing on heparanase-related molecules namely, cathepsin L and heparanase 2 (Hpa2), a heparanase homolog.
authors.affiliation: Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, P. O. Box 9649, Haifa, 31096, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Arvatz
authors.forename: Itay
authors.initials: I
authors.lastname: Shafat
authors.forename: Flonia
authors.initials: F
authors.lastname: Levy-Adam
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
mesh_terms: D000595:Amino Acid Sequence; D056668:Cathepsin L / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000099175:Heparanase
chemical_list: D056668:Cathepsin L; D005966:Glucuronidase; D000099175:Heparanase