Extracellular matrix components and hyaluronic acid–binding cell surface receptors (ECM/HA-binding receptors)

Extracellular matrix (ECM) components and hyaluronic acid (HA)-binding cell surface receptors constitute a complex network essential for maintaining tissue structural integrity and mediating cellular signaling. The ECM is composed of various macromolecules, including fibrous proteins like collagen and glycosaminoglycans such as hyaluronic acid, which provide physical scaffolding and biochemical cues to cells (Source: PMID: 24441111). HA-binding receptors, or hyaladherins, notably CD44, RHAMM (HMMR), and LYVE1, translate these extracellular signals into intracellular responses that govern cell adhesion, migration, and survival (Source: UniProt P16070, O75330). In many diseases, particularly solid tumors and inflammatory conditions, the ECM undergoes significant remodeling, often characterized by HA accumulation and receptor upregulation, which promotes malignancy and chemoresistance (Source: PMID: 30610223). Therapeutic interventions targeting this axis include hyaluronidases like Pegvorhyaluronidase alfa to degrade the ECM barrier and monoclonal antibodies such as RG7356 to block receptor-ligand interactions (Source: ClinicalTrials.gov). However, the widespread physiological distribution of these components poses significant challenges for achieving therapeutic selectivity and avoiding off-target toxicities.

Other names

HyaladherinsHyaluronan receptorsECM receptorsHA-binding proteins

The primary mechanisms include the enzymatic degradation of hyaluronic acid within the extracellular matrix to reduce interstitial fluid pressure and improve drug delivery, as well as the use of monoclonal antibodies to block the interaction between hyaluronic acid and its receptors, thereby inhibiting pro-survival and migratory signaling pathways.