FROM SERUM TO TISSUE: GALECTIN-BINDING GLYCOFORMS OF SERUM GLYCOPROTEINS AS FUNCTIONAL BIOMARKERS

Abstract: Galectins are small soluble proteins defined by a conserved sequence motif that forms a defining β-galactoside binding site shared among galectins; adjacent binding sites give each galectin a unique fine specificity for a specific subset of galactose containing glycans. A wealth of data now suggests important roles of galectins in both cancer and inflammation. The aim of this project is to get a clearer picture of how these simple proteins can play such a wide variety of roles. Our findings suggest a basic cellular mechanism– galectins use their unique fine specificities to bind and regulate the cellular trafficking of glycoproteins, which could lead to functional effects, such as targeting a glycoprotein to either side of a cell, changing the time it stays at the cell surface, and organizing it relative to other glycoproteins. Coupled to the well-known changes of glycans occurring during pathological conditions, this mechanism predicts a rich and complex array of regulatory functions of the galectins. This will depend on the match between the binding specificity and cellular expression of the galectin and the structure and cellular expression of the glycan.