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Peptide-based interference of the transmembrane domain of neuropilin-1 inhibits glioma growth in vivo

Oncogene volume 29, pages 2381–2392 (2010)Cite this article

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Abstract

Angiogenesis in glioblastoma is largely dependent on vascular endothelial growth factor (VEGF) signalling. Consistently, the VEGF coreceptor NRP1 promotes angiogenesis and tumour growth in gliomas. Here, we provide data showing that an innovative peptidic tool targeting the transmembrane domain of NRP1 efficiently blocks rat and human glioma growth in vivo. We show both in vivo and in vitro that the antitumour effect results from the anti-proliferative, anti-migratory and anti-angiogenic properties of the compound. The proposed NRP1 antagonizing peptide is therefore a promising novel class of anti-angiogenic drugs that might prolong glioma patient survival. Our results finally show for the first time that the transmembrane domain of important signalling receptors can be antagonized in vivo thereby providing a new avenue towards the development of atypical antagonists with strong therapeutic potential.

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Acknowledgements

We thank Dr Sophie Reibel-Foisset and Mr Nicolas Lethenet for excellent assistance with in vivo experiments and animal care. This work was supported by INSERM, ACI JC (No. 5327), ARC, ANR Emergence bio, FRC/Rotary international to Dominique Bagnard. Cécile Nasarre was supported by Pharmaxon and La Ligue Contre le Cancer.

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Authors and Affiliations

  1. INSERM U575, Physiopathologie du Système Nerveux, Strasbourg, France

    C Nasarre, M Roth, L Jacob, L Roth, E Koncina, A Thien, G Labourdette, G Crémel, G Roussel, D Aunis & D Bagnard

  2. Laboratoire de Neuroimagerie et Neurosciences Cognitives, Institut de Physique Biologique, Strasbourg, France

    P Poulet

  3. LISM, CNRS UPR 9027, Marseille, France

    P Hubert

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  1. C Nasarre
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Correspondence to D Bagnard.

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Nasarre, C., Roth, M., Jacob, L. et al. Peptide-based interference of the transmembrane domain of neuropilin-1 inhibits glioma growth in vivo. Oncogene 29, 2381–2392 (2010). https://doi.org/10.1038/onc.2010.9

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