Fibroblast growth factor–heparan sulfate interaction (FGF-HS)

The interaction between Fibroblast Growth Factors (FGFs) and heparan sulfate (HS) proteoglycans is a fundamental regulatory mechanism in mammalian cell signaling (Ornitz & Itoh, 2015, PubMed: 25744309). Heparan sulfate acts as an essential co-receptor that facilitates the dimerization of FGF ligands and their subsequent binding to Fibroblast Growth Factor Receptors (FGFRs), forming a stable ternary complex (Schlessinger et al., 2000, PubMed: 10821264). This interaction is crucial for protecting FGFs from proteolytic degradation and for sequestering them within the extracellular matrix, creating a reservoir of growth factors (Pellegrini, 2001, PubMed: 11483357). In pathological states, particularly cancer, the FGF-HS interaction is often hijacked to drive tumor-induced angiogenesis, cell survival, and metastasis (Presta et al., 2005, PubMed: 15905528). Therapeutic interventions targeting this interaction include heparin mimetics like Muparfostat, which competitively inhibit FGF binding to HS, thereby dampening downstream signaling (Pisano et al., 2014, PubMed: 24513309). Additionally, inhibitors of heparanase are used to prevent the release of HS-bound FGFs from the matrix (Hammond et al., 2014, PubMed: 24631437). Despite its therapeutic potential, targeting this interaction requires careful management of off-target effects, such as interference with blood coagulation pathways (Dredge et al., 2010, PubMed: 20143215).

Other names

Fibroblast growth factor–heparan sulfate proteoglycan interactionFGF-HSPG interactionFGF-heparin interactionFGF-HS-FGFR ternary complex formation

Competitive inhibition of the formation of the FGF-HS-FGFR ternary signaling complex by mimicking heparan sulfate to sequester FGF ligands or by blocking the heparan sulfate-binding site on FGF proteins.