1. ¹Department of Surgery, Royal College of Surgeons in Ireland, Education & Research Centre, Beaumont Hospital, Dublin 9, Ireland
2. ²Centre for Synthesis & Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland
3. ³School of Biology and Biochemistry, Medical Biology Centre, Queen's University of Belfast, Northern Ireland

Correspondence: Dr JH Harmey, E-mail: jharmey@rcsi.ie

⁴Both these authors contributed equally to this study

Received 23 June 2004; Revised 20 October 2004; Accepted 8 November 2004; Published online 18 January 2005.

Abstract

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.