Submitted on February 15, 2008
Accepted on February 20, 2008
Ganglioside GM3 suppresses the pro-angiogenic effects of vascular endothelial growth factor and ganglioside GD1A
Purna Mukherjee, Anthony C. Faber, Laura M. Shelton, Rena C. Baek, Thomas C. Chiles, and Thomas N. Seyfried
Department of Biology, Boston College, Chestnut Hill, MA 02467
Corresponding Author: thomas.seyfried{at}bc.edu
Gangliosides are sialic acid-containing glycosphingolipids that have long been associated with tumor malignancy and metastasis. Mounting evidence suggests that gangliosides also modulate tumor angiogenesis. Tumor cells shed gangliosides into the microenvironment, which produces both autocrine and paracrine effects on tumor cells and tumor associated host cells. In this study, we show that the simple monosialo-ganglioside GM3 counteracts the pro-angiogenic effects of vascular endothelial growth factor (VEGF) and of the complex disialo-ganglioside GD1a. GM3 suppressed the action of VEGF and GD1a on the proliferation of human umbilical vein endothelial cells (HUVEC), and inhibited the migration of HUVEC towards VEGF as a chemoattractant. Enrichment of added GM3 in the HUVEC membrane also reduced phosphorylation of VEGF receptor 2 (VEGFR-2) and downstream Akt. Moreover, GM3 reduced the pro-angiogenic effects of GD1a and growth factors in the in vivo Matrigel plug assay. Inhibition of GM3 biosynthesis with the glucosyl transferase inhibitor, N-butyldeoxynojirimycin (NB-DNJ), increased HUVEC proliferation and phosphorylation of VEGFR-2 and Akt. The effects of NB-DNJ on HUVEC were reversed with addition of GM3. We conclude that GM3 has anti-angiogenic action and may possess therapeutic potential for reducing tumor angiogenesis.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
