HPSE

HPSE, or heparanase, is an endo-beta-D-glucuronidase enzyme that cleaves heparan sulfate (HS) chains on heparan sulfate proteoglycans in the extracellular matrix and on cell surfaces. In humans, HPSE is encoded by the HPSE gene. The enzyme is produced as a latent 65-kDa proenzyme and is secreted or transported to lysosomes, where proteolytic processing generates an active heterodimer that cleaves HS chains, enabling remodeling of the extracellular matrix and basement membranes.

Functionally, HPSE releases HS-bound growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGFs), promoting angiogenesis and tissue remodeling. By loosening ECM barriers and liberating signaling molecules, HPSE facilitates cell invasion and metastasis in cancer and contributes to inflammatory responses and wound healing. It also plays a role in normal development and tissue homeostasis.

Regulation of HPSE occurs at multiple levels, including transcriptional control and post-translational processing. Inhibitors of HPSE include endogenous regulators such as HPSE2, which can suppress HPSE activity, and pharmacologic inhibitors such as heparan sulfate mimetics. Several HPSE inhibitors have been explored in preclinical and clinical settings as potential anti-cancer or anti-fibrotic therapies.

Clinical relevance of HPSE centers on its association with tumor progression and metastasis; higher HPSE expression or activity is observed in various cancers and is often linked to poorer prognosis. Because of its central role in matrix remodeling and growth factor release, HPSE is investigated as a therapeutic target and as a biomarker in certain diseases, including inflammatory conditions.

See also: Heparanase-2 (HPSE2).