title: Mammalian heparanase: involvement in cancer metastasis, angiogenesis and normal development.
abstract: Cleavage of heparan sulphate proteoglycans (HSPGs) affects the integrity and functional state of tissues and thereby fundamental normal and pathological phenomena involving cell migration and response to changes in the extracellular microenvironment. Heparanase, degrading heparan sulphate (HS) at specific intrachain sites, is synthesized as a latent approximately 65 kDa protein that is processed at the N-terminus into a highly active approximately 50 kDa form. The heparanase enzyme is preferentially expressed in human tumours and its overexpression in low-metastatic tumour cells confers a highly invasive phenotype in experimental animals. Heparanase also releases angiogenic factors and accessory fragments of HS from the tumour microenvironment and induces an angiogenic response in vivo. Heparanase may thus facilitate tumour cell invasion, vascularization and survival in a given microenvironment, all critical events in cancer progression. These observations, the anticancerous effect of heparanase-inhibiting molecules, and the unexpected identification of a single predominant functional heparanase suggest that the enzyme is a promising target for drug development.
authors.affiliation: Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel. vlodavsk@cc.huji.ac.il
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Orit
authors.initials: O
authors.lastname: Goldshmidt
authors.forename: Eyal
authors.initials: E
authors.lastname: Zcharia
authors.forename: Ruth
authors.initials: R
authors.lastname: Atzmon
authors.forename: Zehava
authors.initials: Z
authors.lastname: Rangini-Guatta
authors.forename: Michael
authors.initials: M
authors.lastname: Elkin
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.forename: Yael
authors.initials: Y
authors.lastname: Friedmann
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002455:Cell Division; D018450:Disease Progression; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D000099175:Heparanase