Peptide-based interference of the transmembrane domain of neuropilin-1 inhibits glioma growth in vivo.
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.
Nasarre
C
C
INSERM U575, Physiopathologie du Système Nerveux, Strasbourg, France.
Roth
M
M
Jacob
L
L
Roth
L
L
Koncina
E
E
Thien
A
A
Labourdette
G
G
Poulet
P
P
Hubert
P
P
Crémel
G
G
Roussel
G
G
Aunis
D
D
Bagnard
D
D
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D039942:Neuropilin-1