Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis
| العنوان: | Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis |
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| المؤلفون: | José Courty, Isabelle Bernard-Pierrot, Jean Plouët, Yamina Hamma-Kourbali, Panagiotis Katsoris, Denis Barritault, Jean Delbé, Evangelia Papadimitriou, Mélanie Héroult |
| المصدر: | Oncogene. 23:1745-1753 |
| بيانات النشر: | Springer Science and Business Media LLC, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Cancer Research, Angiogenesis, Amino Acid Motifs, Neovascularization, Physiologic, Biology, Protein Structure, Secondary, chemistry.chemical_compound, Cell Movement, Genetics, Neuropilin, Humans, Receptor, Molecular Biology, Cells, Cultured, Tube formation, Matrigel, Thrombospondin, Heparin, Endothelial Cells, Cell Differentiation, Protein Structure, Tertiary, Cell biology, Vascular endothelial growth factor, Drug Combinations, Receptors, Vascular Endothelial Growth Factor, chemistry, Biochemistry, Cytokines, Proteoglycans, Collagen, Laminin, Carrier Proteins, Tyrosine kinase, Cell Division, Protein Binding |
| الوصف: | Heparin affin regulatory peptide (HARP) is an heparin-binding molecule involved in the regulation of cell proliferation and differentiation. Here, we report that HARP inhibited the biological activity induced by the 165-amino-acid form of vascular endothelial growth factor (VEGF165) on human umbilical vein endothelial cells. Endothelial-cell proliferation induced by VEGF165 showed about 50% inhibition in the presence of HARP in a concentration of 3 nM. In similar range of concentrations, HARP blocked tube formation induced by VEGF165 in three-dimensional angiogenesis assay. In vivo studies showed that HARP inhibited the VEGF165-induced Matrigel trade mark infiltration of endothelial cells. We then investigated the mechanisms of this inhibition and shown that HARP inhibited the binding of 125I-VEGF165 to the VEGF receptors of endothelial cells. Additional studies using VEGF soluble receptors indicated that binding of 125I-VEGF165 to kinase insert domain-containing receptor and neuropilin receptor was inhibited by HARP, but conversely the binding of 125I-VEGF165 to fms-like tyrosine kinase I receptor was unaffected. A competitive affinity-binding assay demonstrated that HARP interacted directly with VEGF165 with a dissociation coefficient of 1.38 nM. Binding assay using deletion mutants of HARP revealed that the thrombospondin type-1 repeats domains were involved in this interaction. These data demonstrate for the first time that the angiogenic factor HARP can also negatively regulates the angiogenic activity of VEGF165. |
| تدمد: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1206879 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3bdfc401e1509da1e1a83d02874deee9 https://doi.org/10.1038/sj.onc.1206879 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3bdfc401e1509da1e1a83d02874deee9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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| DOI: | 10.1038/sj.onc.1206879 |