Heparanase

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

Synthesis and structure
The protein is originally synthesised in an inactive 65 is_associated_with::kDa proheparanase form in the is_associated_with::golgi apparatus and transferred to late is_associated_with::endosomes/is_associated_with::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 is_associated_with::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
 * an 8 kDa proheparanase fragment and
 * a 50 kDa proheparanase fragment

Function
Heparanase has is_associated_with::endoglycosidase activity and cleaves polymeric is_associated_with::heparan sulfate molecules at sites which are internal within the polymeric chain. In ocular surface physiology this activity functions as an off/on switch for the prosecretory mitogen is_associated_with::lacritin. Lacritin binds the cell surface heparan sulfate proteoglycan is_associated_with::syndecan-1 only in the presence of active heparanase. Heparanase partially or completely cleaves is_associated_with::heparan sulfate to expose a binding site in the N-terminal 50 amino acids of is_associated_with::syndecan-1.

Clinical significance
The successful penetration of the endothelial cell layer that lines the interior surface of is_associated_with::blood vessels is an important process in the formation of blood borne tumour is_associated_with::metastases. is_associated_with::Heparan sulfate is_associated_with::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 is_associated_with::cell lines. Due to the contribution of heparanase activity to metastasis and also to angiogenesis, the inhibition of heparanase activity it is considered to be a potential target for anti-cancer therapies.

Heparanase has been shown to promote arterial thrombosis and stent thrombosis in mouse models due to the cleavage of anti-coagulant is_associated_with::heparan sulfate is_associated_with::proteoglycans.