These authors contributed equally to this work.
Neuropilin-1 expression in cancer and development†
Version of Record online: 25 OCT 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 226, Issue 1, pages 50–60, January 2012
How to Cite
Jubb, A. M., Strickland, L. A., Liu, S. D., Mak, J., Schmidt, M. and Koeppen, H. (2012), Neuropilin-1 expression in cancer and development. J. Pathol., 226: 50–60. doi: 10.1002/path.2989
No conflicts of interest were declared.
- Issue online: 1 DEC 2011
- Version of Record online: 25 OCT 2011
- Accepted manuscript online: 31 AUG 2011 10:27AM EST
- Manuscript Accepted: 23 AUG 2011
- Manuscript Revised: 5 AUG 2011
- Manuscript Received: 24 MAR 2011
- in situ hybridization;
Neuropilin (NRP)-1 is a co-receptor for vascular endothelial growth factor (VEGF). Preclinical data suggest that blockade of NRP1 suppresses tumour growth by inhibiting angiogenesis, in addition to directly inhibiting tumour cell proliferation in certain models. A humanized monoclonal antibody to NRP1 is currently being evaluated as a potential anti-cancer therapy in clinical trials. However, the expression of NRP1 in cancer and physiological angiogenesis has yet to be systematically described. Here we characterize the in situ expression of NRP1 in human cancer and during mammalian development. A monoclonal antibody to human NRP1 was generated and validated for immunohistochemistry by western blotting, use of formalin-fixed cell pellets transfected with NRP1, immunofluorescence, and comparison with in situ hybridization. NRP1 expression was assessed in whole sections of 65 primary breast carcinomas, 95 primary colorectal adenocarcinomas, and 90 primary lung carcinomas. An additional 59 human metastases, 16 xenografts, and three genetically engineered mouse tumour models were also evaluated. Immunoreactivity for NRP1 was seen in vessels from normal tissues adjacent to cancer and in 98–100% of carcinomas. Tumour cell expression of NRP1 was also observed in 36% of primary lung carcinomas and 6% of primary breast carcinomas, but no colorectal adenocarcinomas. NRP1 was evaluated in mouse embryos, where expression was limited to the nervous system, endocardium, vascular smooth muscle, and, focally, endothelium on subsets of vessels. Moreover, in a model of VEGF-dependent angiogenesis in the postnatal mouse trachea, blockade of NRP1 signalling resulted in defective angiogenesis and recapitulated the effects of anti-VEGF treatment. These observations confirm NRP1 as a valid anti-angiogenic target in malignancy, and as a potential direct anti-tumour target in a subset of cancers. The data also confirm a role for NRP1 in physiological, VEGF-mediated angiogenesis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.