Extracellular matrix components and hyaluronan-binding proteins (ECM/HABPs)

Extracellular matrix (ECM) components and hyaluronan-binding proteins (HABPs), collectively known as hyaladherins, form a complex structural and functional network essential for tissue integrity and cellular signaling (UniProt P16070; Nature Reviews Cancer, 2014). HABPs include a diverse group of proteins such as CD44, RHAMM, and proteoglycans like aggrecan and versican, which specifically recognize and bind to hyaluronan, a high-molecular-weight glycosaminoglycan (PubMed: 24388214). These interactions are critical for regulating cell proliferation, migration, and adhesion, but they are frequently dysregulated in diseases such as cancer and chronic inflammation, where an over-accumulation of hyaluronan creates a dense physical barrier that promotes tumor progression and limits drug delivery (PubMed: 30604718). Therapeutic interventions targeting this system often involve the use of hyaluronidases, such as Pegvorhyaluronidase alfa, to deplete the ECM stroma or monoclonal antibodies like RG7356 to block HABP-mediated signaling (ClinicalTrials.gov: NCT02715804). While promising for enhancing the efficacy of chemotherapy in stroma-rich tumors, targeting these components requires careful management of safety concerns related to connective tissue homeostasis and wound healing.

Other names

HyaladherinsECM proteinsHyaluronan-binding proteinsHyaluronan-binding domain (HABD) containing proteinsMatrix proteins

Enzymatic degradation of hyaluronan to reduce interstitial fluid pressure; competitive inhibition of receptor-ligand binding (e.g., CD44-HA interaction); modulation of cell-matrix signaling pathways.