Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells

Abstract

Galectin-3 (Gal-3) is a β-galactoside-binding protein that influences various cell functions, including cell adhesion. We focused on the role of Gal-3 as an extracellular ligand mediating cell-matrix adhesion. We used human adipose tissue-derived stem cells and human umbilical vein endothelial cells that are promising for vascular tissue engineering. We found that these cells naturally contained Gal-3 on their surface and inside the cells. Moreover, they were able to associate with exogenous Gal-3 added to the culture medium. This association was reduced with a β-galactoside LacdiNAc (GalNAcβ1,4GlcNAc), a selective ligand of Gal-3, which binds to the carbohydrate recognition domain (CRD) in the Gal-3 molecule. This ligand was also able to detach Gal-3 newly associated with cells but not Gal-3 naturally present on cells. In addition, Gal-3 preadsorbed on plastic surfaces acted as an adhesion ligand for both cell types, and the cell adhesion was resistant to blocking with LacdiNAc. This result suggests that the adhesion was mediated by a binding site different from the CRD. The blocking of integrin adhesion receptors on cells with specific antibodies revealed that the cell adhesion to the preadsorbed Gal-3 was mediated, at least partially, by β1 and αV integrins—namely α5β1, αVβ3, and αVβ1 integrins.

Overcoming Microenvironment-Mediated Chemoprotection through Stromal Galectin-3 Inhibition in Acute Lymphoblastic Leukemia

“…How Gal3 produced by stromal cells can promote BCP-ALL migration is currently not clear, but it could cluster key glycoprotein binding partners such as integrins on the plasma membrane [45] and promote cell polarization and subsequent directed migration. A second possibility is that Gal3 from stroma regulates intracellular events after its uptake by the BCP-ALL cells, as we have previously shown [12] and confirmed (Figure S2).…”

Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy

“…The KEGG pathways also showed that DEGs were enhanced in cytokine-cytokine receptor interactions and chemokine signaling pathways. Laminin, fibronectin and integrins are known ligands for Gal-3, and therefore, Gal-3 may promote pathological fibrotic processes by regulating cell-cell adhesion and cell proliferation ( 49 , 50 ). Therefore, our study may provide some evidence that Gal-3 plays a multifaceted role in the regulation of inflammatory responses to promote cell-cell interactions and adhesions, which contributes to renal fibrosis that is associated with renal failure.…”

Galectin-3 in Kidney Diseases: From an Old Protein to a New Therapeutic Target

“…Gal-3 is found in the plasma membrane of cells where it can modulate the interaction between epithelial cells and extracellular matrix or with other cells [ 28 ]. Its ability to bind with integrins or endothelial adhesive proteins allows adhesion with other cells or the promotion of activation of bond cells [ 29 , 30 , 31 , 32 ]. Gal-3 can also bind with glycoproteins to promote extra-cellular matrix binding [ 28 , 33 ] and create a bridge between Gal-3 and cells [ 34 ].…”