Hyaluronan receptors and extracellular matrix binding partners (HAR/HABP)

Hyaluronan receptors and extracellular matrix binding partners, collectively known as hyaladherins, are a diverse group of proteins that specifically interact with hyaluronic acid (HA), a major glycosaminoglycan of the extracellular matrix (NIH, 1.3.1). This group includes cell surface receptors such as CD44, RHAMM (HMMR), LYVE-1, and HARE (STAB2), as well as matrix-associated proteins like aggrecan, versican, and TSG-6 (NIH, 1.1.1; ResearchGate, 1.2.2). These molecules play critical roles in regulating cell adhesion, migration, proliferation, and survival by transducing signals from the extracellular environment to the intracellular space (NIH, 1.2.1). In pathological conditions, particularly cancer and chronic inflammation, the expression and activity of these receptors are often dysregulated, promoting tumor metastasis, angiogenesis, and tissue fibrosis (NIH, 1.3.2). For instance, CD44 is frequently overexpressed in solid tumors and cancer stem cells, where it facilitates invasion and resistance to apoptosis (NIH, 1.4.4). Consequently, these proteins have become significant therapeutic targets, with strategies ranging from monoclonal antibodies and vaccines to HA-conjugated nanoparticles designed for targeted drug delivery (NIH, 1.4.1; ACS, 1.4.5). Drugs like RG7356 and Bivatuzumab mertansine have been developed to target CD44 specifically, while HA-drug conjugates utilize receptor-mediated endocytosis to deliver cytotoxic payloads (NIH, 1.1.3). Despite their potential, targeting these receptors poses challenges, such as dose-limiting skin toxicities due to the high expression of CD44 in normal epithelial tissues (NIH, 1.1.3).

Other names

HyaladherinsHyaluronan-binding proteinsHABPsHA receptorsHyaluronic acid-binding proteins

Inhibition of HA-receptor binding, receptor-mediated endocytosis for targeted drug delivery, antibody-drug conjugate (ADC) mediated cell killing, and suppression of downstream signaling pathways such as MAPK/ERK and PI3K/Akt.