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A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells

There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neur...

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Autores principales: Barr, M P, Byrne, A M, Duffy, A M, Condron, C M, Devocelle, M, Harriott, P, Bouchier-Hayes, D J, Harmey, J H
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361857/
https://www.ncbi.nlm.nih.gov/pubmed/15655556
http://dx.doi.org/10.1038/sj.bjc.6602308
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author Barr, M P
Byrne, A M
Duffy, A M
Condron, C M
Devocelle, M
Harriott, P
Bouchier-Hayes, D J
Harmey, J H
author_facet Barr, M P
Byrne, A M
Duffy, A M
Condron, C M
Devocelle, M
Harriott, P
Bouchier-Hayes, D J
Harmey, J H
author_sort Barr, M P
collection PubMed
description There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neuropilin (NP) receptors, NP-1 and NP-2. A 24-mer peptide, which binds to neuropilin-1, induced apoptosis of murine and human breast carcinoma cells, whereas a peptide directed against KDR had no effect. Both anti-NP1 and anti-KDR peptides induced endothelial cell apoptosis. Confocal microscopy using 5-(6)-carboxyfluorescein-labelled peptides showed that anti-NP1 bound to both tumour and endothelial cells, whereas anti-KDR bound endothelial cells only. This study demonstrates that NP-1 plays an essential role in autocrine antiapoptotic signalling by VEGF in tumour cells and that NP1-blockade induces tumour cell and endothelial cell apoptosis. Specific peptides can therefore be used to target both autocrine (tumour cells) and paracrine (endothelial cells) signalling by VEGF.
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spelling pubmed-23618572009-09-10 A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells Barr, M P Byrne, A M Duffy, A M Condron, C M Devocelle, M Harriott, P Bouchier-Hayes, D J Harmey, J H Br J Cancer Molecular Diagnostics There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neuropilin (NP) receptors, NP-1 and NP-2. A 24-mer peptide, which binds to neuropilin-1, induced apoptosis of murine and human breast carcinoma cells, whereas a peptide directed against KDR had no effect. Both anti-NP1 and anti-KDR peptides induced endothelial cell apoptosis. Confocal microscopy using 5-(6)-carboxyfluorescein-labelled peptides showed that anti-NP1 bound to both tumour and endothelial cells, whereas anti-KDR bound endothelial cells only. This study demonstrates that NP-1 plays an essential role in autocrine antiapoptotic signalling by VEGF in tumour cells and that NP1-blockade induces tumour cell and endothelial cell apoptosis. Specific peptides can therefore be used to target both autocrine (tumour cells) and paracrine (endothelial cells) signalling by VEGF. Nature Publishing Group 2005-01-31 2005-01-18 /pmc/articles/PMC2361857/ /pubmed/15655556 http://dx.doi.org/10.1038/sj.bjc.6602308 Text en Copyright © 2005 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Barr, M P
Byrne, A M
Duffy, A M
Condron, C M
Devocelle, M
Harriott, P
Bouchier-Hayes, D J
Harmey, J H
A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
title A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
title_full A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
title_fullStr A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
title_full_unstemmed A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
title_short A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
title_sort peptide corresponding to the neuropilin-1-binding site on vegf(165) induces apoptosis of neuropilin-1-expressing breast tumour cells
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361857/
https://www.ncbi.nlm.nih.gov/pubmed/15655556
http://dx.doi.org/10.1038/sj.bjc.6602308
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