Hyaluronan-binding receptors (HARs)

Hyaluronan-binding receptors (HARs) are a diverse group of proteins, including LYVE-1, HARE/Stabilin-2, CD44, and RHAMM, that mediate the biological effects and clearance of hyaluronan (HA), a major glycosaminoglycan of the extracellular matrix (UniProt P52331, Q8WWQ8, P16070). LYVE-1 is primarily expressed in lymphatic endothelial cells and is involved in HA transport from tissues to lymph, while HARE/Stabilin-2 serves as the primary systemic scavenger receptor for HA in the liver and spleen sinusoids (PMID: 11433388, 16103111). CD44 is the most widely studied member, acting as a cell surface adhesion molecule and signaling receptor that regulates cell proliferation and migration. In disease states, these receptors are often upregulated; for instance, CD44 is a well-known marker for cancer stem cells and promotes metastasis, while LYVE-1 is associated with tumor-induced lymphangiogenesis. Therapeutic strategies targeting HARs include monoclonal antibodies to block signaling, HA-drug conjugates for targeted delivery, and small molecules to inhibit HA-receptor interactions. However, the ubiquitous expression of some members like CD44 poses significant challenges regarding off-target toxicity and systemic HA homeostasis.

Other names

Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)Hyaluronan receptor for endocytosis (HARE)Stabilin-2 (STAB2)Cluster of differentiation 44 (CD44)Receptor for hyaluronan-mediated motility (RHAMM)Stabilin-1 (STAB1)Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1)

Antagonism of hyaluronan binding; Receptor-mediated endocytosis of drug conjugates; Inhibition of receptor-mediated signaling