New Advances of Heparanase and Heparanase-2 in Human Diseases.

As we all know, heparanase plays an important role in human diseases. As a kind of endo-β-glucuronidase, heparanase is the known only enzyme in mammals which could degrade heparan sulfate(HS) specifically. HS is a vital component of extracellular matrix(ECM). Heparanase takes effect by cleaving theβ(1,4)-glycosidic between glucosamine residue and glucuronic acid of HS. This cleavage will cause ECM remodelling and HS-linked biological molecules release, including cytokines, growth factors and a lot of biological molecules regulating various pathological activities. Experiments already proved that heparanase gene over-expresses in cancers of gastrointestinal tract, esophagus, breast and so on. Various studies have demonstrated the heparanase's pro-metastatic function and the reduced survival rate of patients could be indicated by high heparanase levels. Besides, pathological processes including procoagulant activities, preeclamptic placentas and inflammation are all verified to be associated with heparanase activity. In recent years, many functions other than pro-tumor effect was found in heparanase and worldwide researchers conducted varieties of experiments to identify the new function of this significant enzyme. Also, these newly-found functions are closely connected to certain cellular activities, for example epithelial to mesenchymal transition (EMT). It has already been demonstrated that EMT is related to some clinical disorders, like renal diseases. Given that heparanase is the only enzyme capable of this function, it could be concluded that heparanase would be a potential and valuable therapy target. This mini-review aims to retrospect literatures about heparanase published in 2017 and 2018 and provide a direction for therapy methods targeting heparanase.