%0 Journal Article %A Barr, Martin P. %A Byrne, Anne Marie %A Duffy, Angela M. %A Condron, Claire M. %A Devocelle, Marc %A Harriott, Patrick %A Bouchier-Hayes, David J. %A Harmey, Judith H. %D 2019 %T A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells. %U https://repository.rcsi.com/articles/journal_contribution/A_peptide_corresponding_to_the_neuropilin-1-binding_site_on_VEGF_165_induces_apoptosis_of_neuropilin-1-expressing_breast_tumour_cells_/10800815 %2 https://repository.rcsi.com/ndownloader/files/19312178 %K Adenocarcinoma %K Animals %K Apoptosis %K Blotting %K Western %K Breast Neoplasms %K Cell Line %K Tumor %K Endothelial Cells %K Flow Cytometry %K Humans %K Mice %K Microscopy %K Confocal %K Neuropilin-1 %K Peptides %K Vascular Endothelial Growth Factor A %K Vascular Endothelial Growth Factor Receptor-2 %K Surgery %X

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.

%I Royal College of Surgeons in Ireland