Title:The Functions of Heparanase in Human Diseases
Volume: 17
Issue: 6
Author(s): Hao Jin and Shaobo Zhou
Affiliation:
Keywords:
Heparanase, function, diseases, tumor, inflammation.
Abstract: 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.
