HA effects are mediated through two receptors, CD44 (also designated HCAM) and the receptor of hyaluronic acid mediated motility (RHAMM). RHAMM, also designated intracellular hyaluronic acid binding protein (IHABP) and CD168, is a matrix receptor, which is linked to the plasma membrane by a GPI anchor and regulates cell motility. RHAMM expression is upregulated in malignant lymphoid tissues and is subsequently implicated in tumor progression and metastasis formation, as well as signal transduction. Although still unclear, RHAMM is thought to exist as several isoforms ranging in size. A variant isoform, designated v4, is a protein that, when over-expressed, is thought to be the cause of transformation and metastasis formation in fibroblasts.
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