INSERM U575, Physiopathologie du Système Nerveux, Strasbourg, France.
Oncogene. 2010 Apr 22;29(16):2381-92. doi: 10.1038/onc.2010.9. Epub 2010 Feb 8.
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.
胶质母细胞瘤中的血管生成在很大程度上依赖于血管内皮生长因子 (VEGF) 信号通路。一致地，VEGF 共受体 NRP1 促进了神经胶质瘤中的血管生成和肿瘤生长。在这里，我们提供的数据表明，一种针对 NRP1 跨膜结构域的创新肽类工具能够有效地抑制大鼠和人类神经胶质瘤在体内的生长。我们在体内和体外均表明，该抗肿瘤作用源自该化合物的抗增殖、抗迁移和抗血管生成特性。因此，所提出的 NRP1 拮抗肽是一种很有前途的新型抗血管生成药物，可能延长神经胶质瘤患者的生存时间。我们的结果最终首次表明，重要信号受体的跨膜结构域可以在体内被拮抗，从而为开发具有强大治疗潜力的非典型拮抗剂提供了一条新途径。
