Bibes Romain, Gobron Stéphane, Vincent François, Mélin Carole, Vedrenne Nicolas, Perraud Aurélie, Labrousse Francois, Jauberteau Marie-Odile, Lalloué Fabrice
EA3842 Cellular Homeostasis and Diseases, University of Limoges, Faculty of Medicine, 87025 Limoges Cedex, France.
Neuronax, Biopôle Clermont-Limagne, 63360 Saint-Beauzire, France.
Oncotarget. 2017 Sep 12;8(49):85969-85983. doi: 10.18632/oncotarget.20837. eCollection 2017 Oct 17.
Angiogenesis plays a critical role in glioblastoma growth and progression. We therefore aimed at evaluating the anti-angiogenic properties of an oligopeptide originating from SCO-spondin (NX) on a model of human glioblastoma. To this end, we studied the impact of NX treatment on human brain endothelial cells (HBMECs) alone or co-cultured with glioblastoma cells (U87-MG) on apoptosis, proliferation, migration and release of angiogenic factors. We further investigated the anti-angiogenic potential of NX on human glioblastoma cells grown on chorio-allantoic membrane (CAM) or in glioblastoma xenografts. The results of our experiments showed that NX treatment impaired the microvascular network and induced a decrease in cell proliferation, vascularization and tumor growth in the CAM model as well as in xenotransplants. Interestingly, our experiments showed that NX impairs HBMECs migration but also regulates the release of angiogenic factors from U87-MG. These results are confirmed by the profiling of NX-treated U87-MG grown on CAM that highlighted modifications of several genes involved in angiogenesis. In conclusion, NX inhibits tumorigenesis by impairing the ability of glioblastoma cells to induce angiogenesis and by inhibiting endothelial cell migration. This molecule might therefore be an interesting candidate for future cancer therapies.
血管生成在胶质母细胞瘤的生长和进展中起着关键作用。因此,我们旨在评估源自脊髓小脑共济失调伴发素(SCO-spondin,NX)的一种寡肽在人胶质母细胞瘤模型上的抗血管生成特性。为此,我们研究了NX处理对单独培养的人脑内皮细胞(HBMECs)或与人胶质母细胞瘤细胞(U87-MG)共培养的HBMECs在凋亡、增殖、迁移及血管生成因子释放方面的影响。我们进一步研究了NX对在绒毛尿囊膜(CAM)上生长的人胶质母细胞瘤细胞或胶质母细胞瘤异种移植瘤的抗血管生成潜力。我们的实验结果表明,在CAM模型以及异种移植实验中,NX处理破坏了微血管网络,并导致细胞增殖、血管化和肿瘤生长减少。有趣的是,我们的实验表明,NX不仅损害HBMECs的迁移,还调节U87-MG中血管生成因子 的释放。对在CAM上生长的经NX处理的U87-MG进行基因分析,突出了几个参与血管生成的基因的改变,从而证实了这些结果。总之,NX通过损害胶质母细胞瘤细胞诱导血管生成的能力和抑制内皮细胞迁移来抑制肿瘤发生。因此,这种分子可能是未来癌症治疗的一个有吸引力的候选药物。