Heparan sulfate proteoglycans and other extracellular matrix components (HSPGs/ECM)

Heparan sulfate proteoglycans (HSPGs) and other extracellular matrix (ECM) components are essential macromolecules that provide structural integrity to tissues and regulate various physiological processes. HSPGs are characterized by a core protein attached to heparan sulfate glycosaminoglycan (GAG) chains, which possess high negative charge densities allowing them to bind numerous proteins, including growth factors, cytokines, and viral particles (Sarrazin et al., 2011, Cold Spring Harb Perspect Biol). These components act as co-receptors and storage depots for signaling molecules, thereby modulating cell proliferation, migration, and differentiation. In pathological conditions such as cancer, the ECM is often dysregulated, promoting tumor progression and metastasis through increased heparanase activity and altered proteoglycan expression (Fuster & Esko, 2005, Genet Dev). Furthermore, many pathogens, including SARS-CoV-2 and Herpes Simplex Virus, exploit HSPGs as initial attachment sites for host cell entry (Clausen et al., 2020, Cell). Pharmacological targeting of these components involves heparin mimetics and heparanase inhibitors aimed at disrupting these interactions to treat cancer, inflammatory diseases, and viral infections.

Other names

HSPGsExtracellular matrixGlycosaminoglycansBasement membrane componentsCell surface proteoglycans

Competitive inhibition of ligand binding to glycosaminoglycan chains and inhibition of enzymatic degradation by heparanase to prevent growth factor release and viral attachment.