Functional Aspects of the Hyaluronan and Chondroitin Sulfate Receptors

Glycosaminoglycans (GAGs) are distinct from other sugars/oligosaccharides in that they are polymers of disaccharide units (Figure 12.1) composed of an amino sugar, N-acetylglucosamine (GlcNAc), or N-acetylgalactosamine (GalNAc), and uronic acid, glucuronic acid (GlcUA), or iduronic acid (IdUA). The exception is keratan sulfate (KS) in which the uronic acid is replaced by the neutral sugar galactose. Initially, GAGs were thought to be just part of an extracellular glue or ground substance that held tissues together and provided a liquid-like space between cells for the transport of nutrients. However, research using new technologies and techniques over the last two decades has revealed that the effects of GAGs on cells are more dynamic than previously thought. In addition to their structural roles, GAGs are fundamentally important as modifi ers of cell behaviors that range from leukocyte recruitment during infl ammation to the complex signaling events that help cancer cells survive during homing and metastasis. Cellular behaviors and responses depend in part on chain length of the GAG as well as GAG-sugar modifi cations such as sulfation and acetylation. Longer GAGs tend to be part of the extracellular matrix (ECM) in which long cable-like structures and networks may support tissue structure through cross-linking with other ECM components. Shorter GAGs or small oligosaccharides of less than 30-50 sugars may interact with cellular receptors to promote cell signaling involving antiapoptosis or immunostimulation [1].