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

• Published in: Oncogene Vol. 29; no. 16; pp. 2381 - 2392
• Main Authors: NASARRE, C, ROTH, M, ROUSSEL, G, AUNIS, D, BAGNARD, D, JACOB, L, ROTH, L, KONCINA, E, THIEN, A, LABOURDETTE, G, POULET, P, HUBERT, P, CREMEL, G
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 22.04.2010
• Subjects: Amino Acid Sequence; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antagonists; Antiangiogenic agents; Biological and medical sciences; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Cancer; Care and treatment; Cell differentiation, maturation, development, hematopoiesis; Cell growth; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chemical properties; Chick Embryo; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic aspects; Glioblastoma; Glioma; Glioma - drug therapy; Glioma - pathology; Gliomas; Glycoproteins; Growth factor receptors; Health aspects; Humans; Medical sciences; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Molecular Sequence Data; Neurology; Neuropilin; Neuropilin-1 - antagonists & inhibitors; Neuropilin-1 - chemistry; Peptides; Physiological aspects; Protein Structure, Tertiary; Rats; Transmembrane domains; Tumors; Tumors of the nervous system. Phacomatoses; Vascular endothelial growth factor; Xenograft Model Antitumor Assays; France; Nervous system diseases; peptide; Peptides; Growth; Carcinogenesis; Angiogenesis; In vivo; Glioma; Central nervous system disease; Tumor; Inhibition; neuropilin; tumour growth
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.9

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.