Abstract
Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules like growth factors, cytokines and enzymes. In addition to being an enzyme, HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on the current knowledge about the different role of HPSE protein exerted by its enzymatic and non-enzymatic activity.
Highlights
Heparanase is an endoglycosidase that cleaves heparan sulphate (HS) chains and whose activity contributes to degradation and remodeling of extracellular matrix (ECM)
It has been proved that HPSE up-regulates the expression of the blood coagulation initiator-tissue factor (TF) and directly enhances its activity, which leads to increased factor Xa production and subsequent activation of the coagulation system
Since many cancer types are associated with increased TF-associated hypercoagulable states, the high HPSE levels produced by cancer sustaining this event create a vicious cycle promoting cancer metastasis
Summary
Heparanase is an endoglycosidase that cleaves heparan sulphate (HS) chains and whose activity contributes to degradation and remodeling of extracellular matrix (ECM). This enzyme is mainly involved in cancer progression [1] but recent studies have added multiple functions to its repertoire [2]. There are two main types of HSPGs linked to ECM: agrin which is abundant in most basal membranes, mainly in the synaptic region and perlecan with a diffuse distribution and a very complex modular structure. The removal of specific sulfate groups by endo-sulfatases and the cleavage of HS chains are other post-biosynthetic modifications of HSPGs. The enzyme that is able to cut HS polysaccharide and release diffusible HS fragments is called heparanase. 5–20 kDa fragments [12]
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