Cell-surface heparan sulfate (HS) (HS)

Cell-surface heparan sulfate (HS) is a complex linear polysaccharide belonging to the glycosaminoglycan family, typically found covalently attached to core proteins to form heparan sulfate proteoglycans (HSPGs) such as syndecans and glypicans (Bishop et al., 2007, Nature Reviews Molecular Cell Biology). These molecules are ubiquitous on the surface of almost all animal cells and within the extracellular matrix, where they serve as critical co-receptors for a wide array of ligands, including growth factors, chemokines, and morphogens (Knelson et al., 2014, Nature Reviews Cancer). By sequestering and presenting signaling molecules like fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs) to their high-affinity receptors, HS plays a fundamental role in regulating developmental signaling, cell proliferation, and tissue homeostasis (Vlodavsky et al., 2012, Matrix Biology). In pathological contexts, HS is frequently exploited by various pathogens, including SARS-CoV-2 and herpes simplex virus, as an initial attachment point for cellular entry (Cagno et al., 2019, Antiviral Chemistry & Chemotherapy). Furthermore, the enzymatic remodeling of HS by heparanase is a key driver of cancer progression, promoting tumor angiogenesis, inflammation, and metastasis (Hammond et al., 2014, Journal of Medicinal Chemistry). Therapeutic strategies targeting HS include the development of HS mimetics that competitively inhibit ligand binding or small molecules that block heparanase activity to disrupt the pro-tumorigenic and pro-viral microenvironment.

Other names

Heparan sulfateHeparan sulfate proteoglycanHSPGCell-surface HSPGMembrane-associated heparan sulfate

Competitive inhibition of ligand binding to cell-surface HS chains and inhibition of heparanase-mediated degradation of the glycocalyx to prevent signaling and metastasis.