In this chapter, we will emphasize the importance of
heparan sulfate proteoglycans (
HSPG) in controlling various physiological and pathological molecular mechanisms and discuss how the
heparanase enzyme can modulate the effects triggered by
HSPG. Additionally, we will also navigate about the existing knowledge of the possible role of heparanase-2 in biological events.
Heparan sulfate is widely distributed and evolutionarily conserved, evidencing its vital importance in cell development and functions such as cell proliferation, migration, adhesion, differentiation, and angiogenesis. During remodeling of the extracellular matrix, the breakdown of
heparan sulfate by
heparanase results in the release of molecules containing anchored
glycosaminoglycan chains of great interest in
heparanase-mediated cell signaling pathways in various physiological states,
tumor development,
inflammation, and other diseases. Taken together, it appears that
heparanase plays a key role in the maintenance of the pathology of
cancer and inflammatory diseases and is a potential target for anti-
cancer therapies. Therefore,
heparanase inhibitors are currently being examined in clinical trials as novel
cancer therapeutics. Heparanase-2 has no enzymatic activity, displays higher affinity for
heparan sulfate and the coding region alignment shows 40% identity with the
heparanase gene. Heparanase-2 plays an important role in embryogenic development however its mode of action and biological function remain to be elucidated. Heparanase-2 functions as an inhibitor of the heparanase-1
enzyme and also inhibits neovascularization mediated by
VEGF. The HPSE2 gene is repressed by the Polycomb complex, together suggesting a role as a
tumor suppressor.