The role of galectins in mediating the adhesion of circulating cells to vascular endothelium

Abstract

Vascular cell adhesion is a complex orchestration of events that commonly feature lectin-ligand interactions between circulating cells, such as immune, stem, and tumor cells, and endothelial cells (ECs) lining post-capillary venules. Characteristically, circulating cell adherence to the vasculature endothelium is initiated through interactions between surface sialo-fucosylated glycoprotein ligands and lectins, specifically platelet (P)- or endothelial (E)-selectin on ECs or between leukocyte (L)-selectin on circulating leukocytes and L-selectin ligands on ECs, culminating in circulating cell extravasation. This lectin-ligand interplay enables the migration of immune cells into specific tissue sites to help maintain effective immunosurveillance and inflammation control, the homing of stem cells to bone marrow or tissues in need of repair, and, unfortunately, in some cases, the dissemination of circulating tumor cells (CTCs) to distant metastatic sites. Interestingly, there is a growing body of evidence showing that the family of β-galactoside-binding lectins, known as galectins, can also play pivotal roles in the adhesion of circulating cells to the vascular endothelium. In this review, we present contemporary knowledge on the significant roles of host- and/or tumor-derived galectin (Gal)-3, -8, and -9 in facilitating the adhesion of circulating cells to the vascular endothelium either directly by acting as bridging molecules or indirectly by triggering signaling pathways to express adhesion molecules on ECs. We also explore strategies for interfering with galectin-mediated adhesion to attenuate inflammation or hinder the metastatic seeding of CTCs, which are often rich in galectins and/or their glycan ligands.

Keywords: cell adhesion; endothelial cells; galectin-3; galectin-8; galectin-9.

Figure 1

Human Galectins. The three major families (Prototypical, Chimera, and Tandem Repeat) of galectins found in humans are categorized by their structural characteristics and ligand selectivity properties.

Figure 2

Galectin-Mediated Cell Adhesion to the Vascular Endothelium. This cartoon depicts the proposed critical role of Gal-3, -8, and -9, secreted into the extracellular space (lumen of a blood vessel) potentially by immune, stem, stromal, parenchymal and/or tumor cell sources, in supporting or ‘bridging’ circulating cell adhesion to vascular ECs. Membrane-bound galectins or galectins in solution can theoretically crosslink glycans, such poly-LacNAcs, displayed by surface glycoprotein ligands on cells to mediate intercellular adhesion. These interactions can then facilitate the transition to firm adhesion and diapedesis of cells into tissues.