Syndecan-2 downregulation impairs angiogenesis in human microvascular endothelial cells |
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Authors: | Oriol Noguer Joan Villena Jordi Lorita Manuel Reina |
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Affiliation: | a Department of Cellular Biology, Faculty of Biology, University of Barcelona, Catalonia, Spain b Department of Nutrition, Faculty of Pharmacy, University of Valparaiso, Valparaiso, Chile c Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Catalonia, Spain |
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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. |
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Keywords: | HSPG, heparan sulphate proteoglycan GAG, glycosaminoglycan FBS, foetal bovine serum GFs, growth factors EGF, epidermal growth factor bFGF, basic fibroblast growth factor VEGF, vascular endothelial growth factor PMA, phorbol 12-myristate-13 acetate EDTA, ethylenediamine tetraacetic acid PMSF, phenylmethylsulphonyl fluoride ERM, Ezrin/Radixin/Moesin family proteins ECM, extracellular matrix PDZ, PSD95/DLG/ZO-1 related proteins |
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