Heparin-binding growth factors and their cell-surface presentation (HBGF-HSPG)

Heparin-binding growth factors and their cell-surface presentation refers to the biological process and molecular assembly where heparan sulfate proteoglycans (HSPGs) act as obligatory co-receptors to facilitate growth factor signaling. This system involves a variety of ligands, most notably the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) families, which bind to the heparan sulfate chains of cell-surface proteoglycans like syndecans and glypicans (Reactome R-HSA-388396). These HSPGs concentrate growth factors at the cell surface, protect them from proteolytic degradation, and are essential for the formation of stable, active signaling complexes with their respective high-affinity receptor tyrosine kinases (Sarrazin et al., 2011, Cold Spring Harb Perspect Biol). Dysregulation of this presentation mechanism is a key driver in cancer progression, where it promotes angiogenesis, tumor cell proliferation, and metastasis (Knelson et al., 2014, Nat Rev Cancer). Therapeutic strategies targeting this interaction include the use of heparin mimetics and heparanase inhibitors, which aim to disrupt the sequestration and presentation of these growth factors to inhibit pathological signaling (Dresselhaus & Ferrone, 2022, J Clin Invest). Notable drugs in this space include heparin, suramin, and investigational agents like muparfostat, though their use is often limited by safety concerns such as bleeding risks and impaired wound healing.

Other names

Heparan sulfate proteoglycan-mediated growth factor signalingHBGF-HSPG signaling pathwayFGF-HSPG-FGFR complex formationHeparan sulfate-mediated growth factor presentation

Inhibition of growth factor sequestration and presentation by heparan sulfate proteoglycans; competitive binding to heparin-binding domains of growth factors; inhibition of heparanase-mediated ligand release.