HYALURONAN-BINDING PROTEINS IN DEVELOPMENT, TISSUE HOMEOSTASIS, AND DISEASE

The high molecular weight glycosaminoglycan hyaluronan plays an import ant role in tissue remodeling during development, normal tissue homeos tasis, and disease. The interaction of hyaluronan with matrix hyaluron an-binding proteins and cell-surface hyaluronan receptors regulates ma ny aspects of cell behavior such as cell migration, cell-cell adhesion , and cell differentiation. Hyaluronan-binding proteins have been grou ped together as a family termed hyaladherins-further subdivided in mat rix and cell-surface hyaladherins (receptors). Specific hyaluronan-hya ladherin interactions that affect cell behavior are the focus of this review. Both clearance and turnover of hyaluronan involve hyaluronan r eceptor-mediated endocytosis. Pericellular matrix assembly and retenti on on many cells, especially chondrocytes, are mediated by hyaluronan receptors, in coordination with other matrix hyaladherins. Hyaluronan can also have an independent, direct effect on cell-to-cell adhesion a s well as migration, again mediated by specific cell-surface hyalurona n receptors. This is especially apparent in tumor cells, where metasta tic potential is correlated with hyaluronan receptor expression. As mi grating cells encounter new environments enriched in matrix hyaladheri ns, the capacity for matrix assembly may terminate cell migration. Thu s, the temporal/spatial deposition of particular matrix hyaladherins a lso serves as signals or matrix cues to alter cell behavior.