Modulation of endothelial cell migration and angiogenesis: a novel function for the “tandem‐repeat” lectin galectin‐8

• Published in: The FASEB journal Vol. 25; no. 1; pp. 242 - 254
• Main Authors: Delgado, Víctor M. Cárdenas, Nugnes, Lorena G., Colombo, Lucas L., Troncoso, María F., Fernández, Marisa M., Malchiodi, Emilio L., Frahm, Isabel, Croci, Diego O., Compagno, Daniel, Rabinovich, Gabriel A., Wolfenstein‐Todel, Carlota, Elola, María T.
• Format: Journal Article
• Language: English
• Published: United States 01-01-2011
• Subjects: Activated-Leukocyte Cell Adhesion Molecule - metabolism; Angiogenesis; Animals; capillary formation; Cell Line; Cell Movement - drug effects; Cell Nucleus - metabolism; Collagen; Cytoplasm - metabolism; Dose-Response Relationship, Drug; Drug Combinations; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - physiology; Female; Galectins - genetics; Galectins - metabolism; Galectins - pharmacology; glycan‐binding proteins; Humans; Immunoblotting; Immunohistochemistry; Immunoprecipitation; invasion; Kinetics; Laminin; Mice; Mice, Inbred BALB C; Neoplasms - blood supply; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Physiologic - drug effects; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Protein Binding; Proteoglycans; Rats; Recombinant Proteins - pharmacology; Vascular Endothelial Growth Factor A - pharmacology
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.09-144907

Angiogenesis, the growth of new capillaries from preexisting blood vessels, is a complex process involving endothelial cell (EC) activation, disruption of vascular basement membranes, and migration and proliferation of ECs. Glycan‐mediated recognition has been proposed to play an instrumental role in mediating cell‐cell and cell‐matrix interactions. Ga‐lectins (Gal), a family of glycan‐binding proteins with affinity for β‐galactosides and a conserved sequence motif, can decipher glycan‐containing information and mediate cell‐cell communication. Galectin‐8 (Gal‐8), a member of this family, is a bivalent “tandem‐repeat”‐type galectin, which possesses 2 CRDs connected by a linker peptide. Here, we show that Gal‐8 is endowed with proangiogeneic properties. Functional assays revealed a critical role for this lectin in the regulation of capillary‐tube formation and EC migration. Moreover, Matrigel, either supplemented with Gal‐8 or vascular endothelial growth factor (VEGF), injected in mice resulted in induction of in vivo angiogenesis. Remarkably, Gal‐8 was expressed both in the cytoplasm and nucleus in ECs of normal and tumor vessels. Furthermore, CD166 [activated leukocyte cell adhesion molecule (ALCAM)] was identified as a specific Gal‐8‐binding partner in normal vascular ECs. Collectively, these data provide the first evidence demonstrating an essential role for Gal‐8 in the regulation of angiogenesis with critical implications in tumor biology.—CCárdenasrdenas Delgado, V. M., Nugnes, L. G., Colombo, L. L., Troncoso, M. F., Fernández, M. M., Malchiodi, E. L., Frahm, I., Croci, D. O., Compagno, D., Rabinovich, G. A., Wolfenstein‐Todel, C., Elola, M. T. Modulation of endothelial cell migration and angiogenesis: a novel function for the “tandem‐repeat” lectin galectin‐8. FASEB J. 25, 242–254 (2011). www.fasebj.org