Heparanase

Editors-In-Chief: William J. Gibson, Massachusetts Institute of Technology, Cambridge MA

Heparanase, also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides.

Synthesis and structure
The protein is originally synthesised in an inactive 65 kDa proheparanase form in the golgi apparatus and transferred to late endosomes/lysosomes for transport to the cell-surface. In the lysosome it is proteolytically processed into its active form. Proteolytic processing results in the production of three products, The 8 kDa and 50 kDa fragments form a heterodimer and it is this heterodimer that constitutes the active heparanase molecule. The linker protein is so called because prior to its excision it physically links the 8 kDa and 50 kDa proheparanase fragments. Complete excision of the linker peptide appears to be a prerequisite to the complete activation of the heparanase enzyme.
 * a linker peptide
 * a 8 kDa proheparanase fragment and
 * a 50 kDa proheparanase fragment

Endoglycosidic action
Heparanase cleaves polymeric heparan sulfate molecules at sites which are internal within the polymeric chain.

Role in metastasis and angiogenesis
The successful penetration of the endothelial cell layer that lines the interior surface of blood vessels is an important process in the formation of blood borne tumour metastases. Heparan sulfate proteoglycans are major constituents of this layer and it has been shown that increased metastatic potential corresponds with increased heparanase activity for a number of cell lines. Due to the contribution of heparinase activity to metastasis and also to angiogenesis, the inhibition of heparinase activity it is considered to be a potential target for anti-cancer therapies.

Heparanase Inhibitors

 * Heparin and low molecular weight heparin
 * Suramin
 * Calcium spirulan
 * Phosphomannopentaose sulfate (PI-88)
 * Maltohexaose sulfate
 * Laminarin sulfate
 * Anti-heparanase antibodies