Purpose: Heparanase promotes myeloma growth, dissemination, and angiogenesis through modulation of the tumor microenvironment, thus highlighting the potential of therapeutically targeting this enzyme. SST0001, a nonanticoagulant heparin with antiheparanase activity, was examined for its inhibition of myeloma tumor growth in vivo and for its mechanism of action. Experimental Design: The ability ...

Heparan sulphate proteoglycans are ubiquitous macromolecules of cell surfaces and extracellular matrices. Numerous extracellular matrix proteins, growth factors, morphogens, cytokines, chemokines and coagulation factors are bound and regulated by heparan sulphate. Degradation of heparan sulphate thus potentially profoundly affects cell and tissue function. Although there is evidence that severa...

Blood vessels are highly active structures whose morphology rapidly adapts to maintain vascular function under altered systemic and local conditions. In some instances, this normally beneficial adaptation may be detrimental to overall function. Structural adaptations with important physiological and pathophysiological impact include angiogenesis, the remodeling of resistance arteries, and steno...

Endoglycosidic heparan-sulfate-degrading heparanase has important roles in a variety of biological processes, including angiogenesis, inflammation, wound healing and metastatsis (Dempsey et al., 2000a; Irimura et al., 1986; Parish et al., 2001; Vlodavsky et al., 1990; Vlodavsky et al., 1994). A predominant cDNA encoding heparanase was independently cloned by several groups, and its gene localiz...

Extracellular matrix (ECM) and basement membranes (BMs) present a physical barrier that requires enzymatic degradation during endothelial cell (EC) sprouting at early stages of angiogenesis. These multimolecular structures also serve as a storage depot for heparin-binding angiogenic factors. Heparan sulfate proteoglycans (HSPGs) are responsible for the self-assembly and integrity of the ECM and...

STUDY QUESTION What is the effect of estrogen on heparanase procogulant activity? SUMMARY ANSWER Estrogen increases heparanase procoagulant activity. WHAT IS KNOWN ALREADY Estrogen therapy increases the risk of thrombosis and was previously found to up-regulate heparanase expression. Heparanase is involved in angiogenesis and metastasis, and has been shown to form a complex with tissue fact...

The tetrasaccharide heparan sulfate (HS) mimetic PG545, a clinical anti-cancer candidate, is an inhibitor of the HS-degrading enzyme heparanase. The kinetics of heparanase inhibition by PG545 and three structural analogues were investigated to understand their modes of inhibition. The cholestanol aglycon of PG545 significantly increased affinity for heparanase and also modified the inhibition m...

Oral mucosal melanoma is an aggressive neoplasm with poor prognosis. Heparanase is an endo-beta-d-glucuronidase, which cleaves heparan sulphate chains. The vascular endothelial growth factor (VEGF) is the most potent angiogenic mitogen and interaction with its receptor (VEGFR) has been associated with angiogenesis. We investigated the expression of these molecules in the progression of oral muc...

The physicochemical characteristics of the glomerular capillary filtration membrane restrict the passage of macromolecules on the basis of molecular weight, charge, and shape. The proposed ionic charge permselectivity characteristics of the glomerular basement membrane (GBM) are determined by its chemical composition, primarily the highly sulfated glycosaminoglycan heparan. In diabetic nephropa...

Increased expression of lymphangiogenesis factors VEGF-C/D and heparanase has been correlated with the invasion of cancer. Furthermore, chemokines may modify matrix to facilitate metastasis, and they are associated with VEGF-C and heparanase. The chemokine CXCL7 binds heparin and the G-protein-linked receptor CXCR2. We investigated the effect of CXCR2 blockade on the expression of VEGF-C/D, hep...