The Functions of Heparanase in Human Diseases

The study of the heparanase has long been paid wide attention. Heparanase, an endo-β-D-glucuronidase, is capable of specifically degrading heparan sulfate (HS), one of the excellular matrix (ECM) components. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion. Varieties of experiments indicated that heparanase mRNA is overexpressed in human tumors, including breast cancer, gastrointestinal tumors, and esophageal carcinomas. A pro-metastatic and pro-angiogenic role for heparanase has been widely verified and high levels of heparanase correlate with reduced survival of cancer patients. Except protumor function, heparanase also plays a role in inflammation, angiogenesis, placentas and procoagulant activities. Heparanase is found to have many other functions in recent years, since many experiments have been carried out to identify this significant enzyme's new features. These newly found functions are related to the cellular activities such as autophagy and epithelial to mesenchymal transition (EMT). And together with other heparanase functions, autophagy and EMT are verified to be involved in several clinical disorders, for example, renal diseases. Considering that, once inactivated, there are no other enzymes capable of performing the same function, it is apparent that heparanase can be an effective and promising therapy target. This short review aims to establish the currently known function of this enzyme and provide evidence for heparanase targeted therapy.