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The impact of heparanase on cancer
progression
Vlodavsky I,1 Ilan N,1 Abboud-Jarrous
G,2 Nadir Y,1 Brenner B,3 Naggi
A,4 Pisano C,5 Casu B4
1Cancer and Vascular Biology Research Center, The Bruce
Rappaport Faculty of Medicine, Technion, Haifa, Israel; 2Department of Oncology, Hadassah-Hebrew University
Medical Center, Jerusalem, Israel; 3Department of
Hematology, Rambam Medical Center, Haifa, Israel; 4G.
Ronzoni Institute for Chemical and Biochemical Research, Milan,
Italy; 5Sigma-Tau Research Department, Rome, Italy
Background
Heparanase is an endo-b-D-glucuronidase involved in cleavage of
heparan sulfate (HS) and hence in degradation and remodeling of the
extracellular matrix (ECM).1,2 Heparanase activity has
been traditionally correlated with the metastatic potential of
tumor-derived cell types and with cell invasion associated with
autoimmunity, inflammation, and angiogenesis. The heparanase gene
and protein are over-expressed in a variety of human primary
tumors, including those of the bladder, breast, prostate, colon,
gastrointestinal system, oral cavity, esophagous, pancreas, and
ovary, as well as in multiple myeloma and acute myeloid
leukemia.1,2 Heparanase upregulation is often correlated
with increased tumor vascularity and poor postoperative survival of
cancer patients. These observations, the anti-cancerous effect of
heparanase gene silencing3 and of heparanase-inhibiting
molecules4 and the unexpected identification of a single
predominant functional heparanase, suggest that the enzyme is a
promising target for anti-cancer drug development. [>Read full article in PDF]