Syndecan-2 Downregulation Impairs Angiogenesis in Human Microvascular Endothelial Cells

Exp Cell Res. 2009 Mar 10;315(5):795-808. doi: 10.1016/j.yexcr.2008.11.016. Epub 2008 Dec 3.

Abstract

The formation of new blood vessels, or angiogenesis, is a necessary process during development but also for tumour growth and other pathologies. It is promoted by different growth factors that stimulate endothelial cells to proliferate, migrate, and generate new tubular structures. Syndecans, transmembrane heparan sulphate proteoglycans, bind such growth factors through their glycosaminoglycan chains and could transduce the signal to the cytoskeleton, thus regulating cell behaviour. We demonstrated that syndecan-2, the major syndecan expressed by human microvascular endothelial cells, is regulated by growth factors and extracellular matrix proteins, in both bidimensional and tridimensional culture conditions. The role of syndecan-2 in "in vitro" tumour angiogenesis was also examined by inhibiting its core protein expression with antisense phosphorothioate oligonucleotides. Downregulation of syndecan-2 reduces spreading and adhesion of endothelial cells, enhances their migration, but also impairs the formation of capillary-like structures. These results suggest that syndecan-2 has an important function in some of the necessary steps that make up the angiogenic process. We therefore propose a pivotal role of this heparan sulphate proteoglycan in the formation of new blood vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Culture Techniques
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelial Cells / physiology
  • Heparan Sulfate Proteoglycans / genetics
  • Heparan Sulfate Proteoglycans / metabolism
  • Heparan Sulfate Proteoglycans / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Microcirculation / drug effects
  • Microcirculation / genetics
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics*
  • Oligonucleotides, Antisense / pharmacology
  • Syndecan-2 / antagonists & inhibitors
  • Syndecan-2 / genetics*
  • Syndecan-2 / metabolism
  • Syndecan-2 / physiology

Substances

  • Heparan Sulfate Proteoglycans
  • Intercellular Signaling Peptides and Proteins
  • Oligonucleotides, Antisense
  • Syndecan-2