Heparanase: one molecule with multiple functions in cancer progression.
Mammalian heparanase, an endoglycosidase-degrading heparan sulfate, is synthesized as a latent 65 kDa precursor that undergoes proteolytic processing, primarily by cathepsin-L, yielding 8 kDa and 50 kDa subunits that heterodimerize to form a highly active enzyme. Enhanced heparanase expression in human tumors correlates with metastatic potential, tumor vascularity, and reduced postoperative survival of cancer patients, attributed to enzymatic and nonenzymatic activities of the heparanase protein. Urinary and plasma levels of heparanase are elevated in cancer patients and suppressed in response to effective anticancer treatments. These observations and the anticancerous effect of heparanase gene silencing and of heparanase-inhibiting molecules suggest that the enzyme is a promising target for anticancer drug development.
Vlodavsky
Israel
I
Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Elkin
Michael
M
Abboud-Jarrous
Ghada
G
Levi-Adam
Flonia
F
Fuks
Liat
L
Shafat
Itay
I
Ilan
Neta
N
D000818:Animals; D018450:Disease Progression; D005966:Glucuronidase / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D011494:Protein Kinases / Q000378:metabolism*; D000099175:Heparanase
D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D036341:Intercellular Signaling Peptides and Proteins; D011494:Protein Kinases; D000099175:Heparanase