Modulation of endothelial cell migration and angiogenesis: A novel function for the ‛tandem-repeat’ lectin galectin-8

CÁRDENAS-DELGADO VM, COLOMBO LL, TRONCOSO MF, NUGNES LG, FERNÁNDEZ MM, MALCHIODI EL, FRAHM I, CROCI DO, COMPAGNO D, RABINOVICH GA, WOLFENSTEIN-TODEL C, ELOLA MT

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Año: 2011 vol. 25 p. 242 - 254

0892-6638

Angiogenesis, the growth of new capillaries from pre-existing blood vessels, is a complex process involving endothelial cell (EC) activation, disruption of vascular basement membranes, 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 â-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 two CRDs connected by a linker peptide. Here, we show that Gal-8 is endowed with pro-angiogeneic 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 (ALCAM, activated leukocyte cell adhesion molecule) 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.