Modulation of endothelial cell migration and angiogenesis: a novel function for the "tandem-repeat" lectin galectin-8.
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. Galectins (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.
Delgado
Víctor M Cárdenas
VM
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (C1113), Buenos Aires, Argentina.
Nugnes
Lorena G
LG
Colombo
Lucas L
LL
Troncoso
María F
MF
Fernández
Marisa M
MM
Malchiodi
Emilio L
EL
Frahm
Isabel
I
Croci
Diego O
DO
Compagno
Daniel
D
Rabinovich
Gabriel A
GA
Wolfenstein-Todel
Carlota
C
Elola
María T
MT
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D003094:Collagen; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D037161:Galectins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007700:Kinetics; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011485:Protein Binding; D011509:Proteoglycans; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020410:Activated-Leukocyte Cell Adhesion Molecule; D004338:Drug Combinations; D037161:Galectins; C091991:LGALS8 protein, human; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen