Editorial: Interaction Between Hyaluronic Acid and Its Receptors (CD44, RHAMM) Regulates the Activity of Inflammation and Cancer

An old Indian legend tells a story about six blind men who touched an elephant. The first man who touched his leg said: " it is a pillar. " The second man who touched the tail said: " it is a rope. " The third man who touched the trunk of the elephant said: " it is a thick branch of a tree. " The fourth man who touched the ear said: " It is a big hand fan. " The fifth man who touched the belly said: " It is a huge wall. " The sixth man who touched the tusk of the elephant said: " It is a solid pipe. " Each one of them loudly insisted that his claim is the right one. Then wise old man arrived to the place of scene, listened to their arguments and said " all of you are right, but all together you identified an elephant. " Similarly, each one of the 18 chapters of this e-book tells a different, fascinating story about the " biological polygamy " of hyaluronan and its receptors. Yet, this story is focused on the author's specific field of interest or discipline. On the other hand, when the 18 chapters are collected in one e-book, each of them fosters the others and collectively a complete scene is created. Hyaluronan or hyaluronic acid (HA), which resides in the interstitial collagenous matrices, increases viscosity and hydration and binds to a " link module motif " of HA-binding proteoglycans (e.g., CD44) and link proteins. HA is a non-sulfated, linear glycosaminoglycan (GAG) composed of repeating disaccharides of (β, 1–4)-glucuronic acid (GlcUA) and (β, 1-3)-N-acetyl glucosamine (GlcNAc). In most tissues, native HA has a high molecular mass of 1000–10,000 kDa, with extended molecular lengths of 2–20 μm. HA plays crucial roles in structuring tissue architecture, in cell motil-ity, in cell adhesion, and in proliferation processes (1, 2). Hyaluronic acid is synthesized by three HA synthase (HAS) proteins. These generate predominantly high molecular weight-HA (HMW-HA) of between 200 and 2000 kDa. HA catabolism is mediated by hyaluronidases, mechanical forces, and oxidative stress (reactive oxygen and nitrogen species). The degradation generates different-sized HA polymers (or fragments), abbreviated low molecular weight-HA (LMW-HA; <200 kDa) and HA oligomers (1). In general (exceptions do exist), LMW-HA is pro-inflammatory and pro-cancerous, whereas HMW-HA is anti-inflammatory and anti-cancerous. In this context, a vicious cycle is generated. Inflammatory conditions …