SCO-spondin oligopeptide inhibits angiogenesis in glioblastoma

// Romain Bibes 1, * , Stephane Gobron 2, * , Francois Vincent 1, 3 , Carole Melin 1 , Nicolas Vedrenne 1 , Aurelie Perraud 1, 4 , Francois Labrousse 1, 5 , Marie-Odile Jauberteau 1, 6 and Fabrice Lalloue 1 1 EA3842 Cellular Homeostasis and Diseases, University of Limoges, Faculty of Medicine, 87025 Limoges Cedex, France 2 Neuronax, Biopole Clermont-Limagne, 63360 Saint-Beauzire, France 3 Limoges University Hospital, Department of Physiological Functional Investigation, 87042 Limoges Cedex, France 4 Limoges University Hospital, Department of Digestive Surgery, 87042 Limoges Cedex, France 5 Limoges University Hospital, Department of Pathology, 87042 Limoges Cedex, France 6 Limoges University Hospital, Department of Immunology, 87042 Limoges Cedex, France * Co-first authorship Correspondence to: Fabrice Lalloue, email: fabrice.lalloue@unilim.fr Keywords: NX peptide, SCO-spondin, TSR, tumor angiogenesis, glioblastoma Received: March 10, 2017     Accepted: August 04, 2017     Published: September 12, 2017 ABSTRACT 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 in vitro 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.