Interaction of Hyaluronan with Proteins and Inflammatory Mediators

7 Interaction of Hyaluronan with Proteins and Inflammatory Mediators 

There is increasing evidence that HA, as well as some further GAGs, play an active role in the development of a variety of diseases by their interaction with different cells and proteins [112]. Although the following list should not be expected to provide a complete survey, the aspects outlined below seem to be particularly important  

HA is able to interact in an autocrine manner with its cell surface receptors that are located on the same cell, i.e. the cell is influenced by a product produced by this cell itself. For instance, it has been recently shown [113] that low-molar-mass HA induces the proteolytic cleavage of CD44 from the surface of tumor cells and promotes tumor cell migration significantly in this manner. 

HA interacts in a paracrine manner with a variety of ECM molecules on neighboring cells, and, due to the size of the HA polysaccharide, one HA molecule is capable of interacting directly with different cells, whereby one HA molecule is able to bind hundreds of ECM proteins. This interaction seems to be very important for the structure and the assembly of many different tissues, particularly for the development of cancer [114]. 

De novo synthesized HA may be secreted from the cell and subsequently interact with different cell surface receptors, such as CD44, the receptor for HA-mediated motility (RHAMM), the HA receptor for endocytosis (HARE) and many others. It has become evident that these processes mediate at least three different, very important physiological processes signal transduction, formation of pericellular coats, and the receptor-mediated internalization. 

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