Modulation of endothelial cell migration and angiogenesis: a novel function for the "tandem-repeat" lectin galectin-8

被引:113
作者
Cardenas Delgado, Victor M. [1 ]
Nugnes, Lorena G. [1 ]
Colombo, Lucas L. [3 ]
Troncoso, Maria F. [1 ]
Fernandez, Marisa M. [2 ]
Malchiodi, Emilio L. [2 ]
Frahm, Isabel [5 ]
Croci, Diego O. [6 ]
Compagno, Daniel [4 ]
Rabinovich, Gabriel A. [4 ,6 ]
Wolfenstein-Todel, Carlota [1 ]
Elola, Maria T. [1 ]
机构
[1] Univ Buenos Aires, Inst Quim & Fis Quim Biol, Fac Farm & Bioquim, Consejo Nacl Invest Cient & Tecn UBA CONICET, Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Catedra Inmunol, Fac Farm & Bioquim,Inst Estudios Inmunidad Humora, Consejo Nacl Invest Cient & Tecn UBA CONICET, Buenos Aires, DF, Argentina
[3] Univ Buenos Aires, Area Invest, Inst Oncolo AH Roffo, Buenos Aires, DF, Argentina
[4] Univ Buenos Aires, Lab Modulac Genet & Inmunol, Dept Quim Biol, Fac Ciencias Exactas & Nat, Buenos Aires, DF, Argentina
[5] Sanatorio Mater Dei, Dept Patol, Buenos Aires, DF, Argentina
[6] Inst Biol & Med Expt IBYME CONICET, Lab Inmunopatol, Buenos Aires, DF, Argentina
关键词
glycan-binding proteins; capillary formation; invasion; CARBOHYDRATE-RECOGNITION; ADHESION MOLECULE; PROSTATE-CANCER; IN-VITRO; EXPRESSION; BINDING; AFFINITY; MORPHOGENESIS; INFLAMMATION; INTEGRINS;
D O I
10.1096/fj.09-144907
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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.-Cardenas Delgado, V. M., Nugnes, L. G., Colombo, L. L., Troncoso, M. F., Fernandez, 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
引用
收藏
页码:242 / 254
页数:13
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