Galectin-8 functions as a matricellular modulator of cell adhesion

The interaction of cells with the extracellular matrix regulates cell adhes ion and motility. Here we demonstrate that different cell types adhere and spread when cultured in serum-free medium on immobilized galectin-8, a mamm alian 13-galactoside-binding protein. At maximal doses, galectin-8 is equip otent to fibronectin in promoting cen adhesion and spreading. Cell adhesion to immobilized galectin-8 is mediated by sugar-protein interactions with i ntegrins, and galectin-8 triggers integrin-mediated signaling cascades incl uding Tyr phosphorylation of focal adhesion kinase and paxillin. Cell adhes ion is potentiated in the presence of Mn2+, whereas it is interrupted in th e presence of soluble galectin-8, integrin beta (1), inhibitory antibodies, EDTA, or thiodigalactoside but not by RGD peptides. Furthermore, cells rea dily adhere onto immobilized monoclonal galectin-8 antibodies, which are eq uipotent to integrin antibodies in promoting cell adhesion. Cell adhesion t o immobilized galectin-8 is partially inhibited by serum proteins, suggesti ng that complex formation between immobilized galectin-8 and serum componen ts generates a matrix that is less supportive of cell adhesion. Accordingly , cell motility on immobilized galectin-8 readily takes place in the presen ce of serum. Truncation of the C-terminal half of galectin-8, including one of its two carbohydrate recognition domains, largely abolishes its ability to modulate cell adhesion, indicating that both carbohydrate recognition d omains are required to maintain a functional form of galectin-8. Collective ly, our findings implicate galectin-8 as a physiological modulator of cell adhesion. When immobilized, it functions as a matrix protein equipotent to fibronectin in promoting cell adhesion by ligation and clustering of cell s urface integrin receptors. In contrast, when present in excess as a soluble ligand, galectin-8 (like fibronectin) forms a complex with integrins that negatively regulates cell adhesion. Because of its dual effects on the adhe sive properties of the cells and its association with fibronectin, galectin -8 might be considered a novel type of matricellular protein.