Hyaluronic acid and glycosaminoglycans (HA/GAGs)

Hyaluronic acid (HA) and related glycosaminoglycans (GAGs) are long, unbranched polysaccharides that serve as primary structural and signaling components of the extracellular matrix (ECM) (PMID: 24388233). HA, a unique non-sulfated GAG, plays a critical role in maintaining tissue hydrodynamics, lubrication, and space-filling, while also modulating cell behavior through receptors like CD44 and RHAMM (PMID: 25448344). In many solid tumors, such as pancreatic ductal adenocarcinoma, the accumulation of HA leads to high interstitial fluid pressure, which collapses blood vessels and creates a physical barrier against the delivery of chemotherapy (PMID: 30611150). Therapeutic interventions targeting this system include the use of hyaluronidases, such as pegvorhyaluronidase alfa, which enzymatically degrade HA to improve drug penetration and oxygenation within the tumor microenvironment (PMID: 29158305). Beyond oncology, GAGs like chondroitin sulfate are utilized in the management of osteoarthritis to support cartilage integrity, and heparin-based GAGs are widely used for their anticoagulant properties due to their interaction with antithrombin (PMID: 11291144). These molecules are also central to wound healing and inflammatory responses, making them versatile targets in regenerative medicine and chronic disease management (PMID: 17022761).

Other names

HyaluronanHyaluronateAcid mucopolysaccharidesGAGsExtracellular matrix polysaccharides

The primary mechanisms include the enzymatic degradation of hyaluronic acid by hyaluronidases to decrease interstitial fluid pressure and enhance chemotherapy delivery, the use of exogenous glycosaminoglycans to restore joint lubrication and cartilage structure, and the competitive inhibition of glycosaminoglycan-receptor interactions to modulate inflammatory and fibrotic signaling pathways.