Heparanase in inflammation and inflammation‐associated cancer

Abstract

Recent years have seen a growing body of evidence that enzymatic remodeling of heparan sulfate proteoglycans profoundly affects a variety of physiological and pathological processes, including inflammation, neovasvularization and tumor development. Heparanase is the sole mammalian endoglycosidase that cleaves heparan sulfate. Extensively studied in cancer progression and aggressiveness, heparanase enzyme was recently implicated in several inflammatory disorders as well. Although the precise mode of heparanase action in inflammatory reactions is still not completely understood, the fact that heparanase activity is mechanistically important both in malignancy and in inflammation argues that this enzyme is a candidate molecule linking inflammation and tumorigenesis in inflammation-associated cancers. The elucidation of the specific effects of heparanase in cancer development, particularly when inflammation is a causal factor, will accelerate the development of novel therapeutic/chemopreventive interventions and help to better define target patient populations in which heparanase-targeting therapies could be particularly beneficial.

Regulation of the Expression of Heparan Sulfate 3‐O‐Sulfotransferase 3B (HS3ST3B) by Inflammatory Stimuli in Human Monocytes

“…Thereby, structural remodeling of HS is likely to play an important role in the regulation of inflammatory and immune responses. An important modulator of HS structure is heparanase, which has been well described to participate in many inflammatory processes via the degradation of HS, both in extracellular space and at the cell surface [Nasser, ; Meirovitz et al, ]. Upstream the action of heparanase, fine regulation of the biosynthesis machinery could be a way to make HS with distinct inflammatory functions.…”

Mechanisms of heparanase inhibitors in cancer therapy

“…81 Heparanase can also release heparan sulfate bound proangiogenic growth factors, bFGF, HGF, PDGF and VEGF, from the extracellular matrix to indirectly promote endothelial cell migration and proliferation. 82,83 Heparanase-induced HS fragments retain biological activity and can enhance growth factor activity. 14,84 Heparanase is preferentially located at the sites of sprouting EC’s, with little evidence of heparanase present on inactive blood vessels.…”

Cancer biology in diabetes

“…Meirovitz et al . reviewed the compelling evidence that heparanase is an important player in coupling inflammation with tumorigenesis, particularly as observed in colitis‐associated colon carcinoma. Several up‐to‐date reviews also nicely summarized the basic and translational aspects related to the involvement of heparanase in cancer progression.…”