Key points are not available for this paper at this time.
Heparanase is a multifunctional molecule having both enzymaticand non-enzymatic functions. Through its endo-β-glucruonidaseactivity, heparanase cleaves heparan sulfate chains of proteoglycansthereby releasing 4–7 kDa fragments of heparan sulfate that canremain biologically active (Freeman and Parish, 1998; Pikas et al.,1998). Heparanase enzyme activity also releases heparin-boundgrowth factors, cytokines, chemokines and other ligands storedwithin the extracellular matrix (ECM). In addition, cleavage ofheparan sulfate contributes to reorganization of the ECM resultingin enhanced cell motility and invasion. Heparanase also performs abroad range of non-enzymatic functions including, for example,upregulation of tissue factor (Nadir et al., 2006), enhancement ofcell adhesion (Levy-Adam et al., 2008), stimulation of Akt signalingand PI3K-dependent endothelial cell migration (Gingis-Velitskiet al., 2004). In addition, through both enzymatic and non-enzymaticactivities, heparanase influences the expression of a number of impor-tant genes including VEGF, HGF and MMP-9 (Zetser et al., 2006;Purushothaman et al., 2008; Ramani et al., 2011) involved in cancerprogression and remodeling of the ECM.There is a single enzymatically active heparanase present in mam-malswhichwasclonedandsequencedin1999byseveralgroupswork-ing independently (Hulett et al., 1999; Kussie et al., 1999; Toyoshimaand Nakajima, 1999; Vlodavsky et al., 1999). Heparanase mRNA codesfor a 61.2 kDa protein containing 543 amino acids. This pro-enzymeform is then cleaved by cathepsin L to generate the active formconsisting of 8 and 50 kDa subunits that associate non-covalently(Abboud-Jarrous et al., 2008). Structurally, heparanase is composed ofa TIM-barrel fold which contains the active site of the enzyme and aC-terminus domain required for secretion and signaling function ofthe protein (Fig. 1)(Fux et al., 2009). Heparanase has a catalytic
Vlodavsky et al. (Fri,) studied this question.