title: Galectin-8 functions as a matricellular modulator of cell adhesion.
abstract: The interaction of cells with the extracellular matrix regulates cell adhesion and motility. Here we demonstrate that different cell types adhere and spread when cultured in serum-free medium on immobilized galectin-8, a mammalian beta-galactoside-binding protein. At maximal doses, galectin-8 is equipotent to fibronectin in promoting cell adhesion and spreading. Cell adhesion to immobilized galectin-8 is mediated by sugar-protein interactions with integrins, and galectin-8 triggers integrin-mediated signaling cascades including Tyr phosphorylation of focal adhesion kinase and paxillin. Cell adhesion is potentiated in the presence of Mn(2+), whereas it is interrupted in the presence of soluble galectin-8, integrin beta(1) inhibitory antibodies, EDTA, or thiodigalactoside but not by RGD peptides. Furthermore, cells readily adhere onto immobilized monoclonal galectin-8 antibodies, which are equipotent to integrin antibodies in promoting cell adhesion. Cell adhesion to immobilized galectin-8 is partially inhibited by serum proteins, suggesting that complex formation between immobilized galectin-8 and serum components generates a matrix that is less supportive of cell adhesion. Accordingly, cell motility on immobilized galectin-8 readily takes place in the presence 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 domains are required to maintain a functional form of galectin-8. Collectively, 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 surface 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 adhesive properties of the cells and its association with fibronectin, galectin-8 might be considered a novel type of matricellular protein.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Levy
authors.forename: R
authors.initials: R
authors.lastname: Arbel-Goren
authors.forename: Y R
authors.initials: YR
authors.lastname: Hadari
authors.forename: S
authors.initials: S
authors.lastname: Eshhar
authors.forename: D
authors.initials: D
authors.lastname: Ronen
authors.forename: E
authors.initials: E
authors.lastname: Elhanany
authors.forename: B
authors.initials: B
authors.lastname: Geiger
authors.forename: Y
authors.initials: Y
authors.lastname: Zick
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D003599:Cytoskeleton / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D037161:Galectins; D006388:Hemagglutinins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D016326:Extracellular Matrix Proteins; D037161:Galectins; D006388:Hemagglutinins; D016023:Integrins