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.
Highlights
Glioblastoma (GBM) is one of the most frequent and lethal forms of brain tumors
Similar apoptotic levels were observed in presence of TSP-1 treatment of Human Brain Microvascular Endothelial Cells (HBMECs) maintained in basal medium (BM) conditions
The present report shows for the first time that a short oligopeptide, NX, derived from a large protein secreted in the central nervous system (CNS), the SCO-spondin, could inhibit angiogenesis ex ovo and in vivo, in a glioblastoma model
Summary
Glioblastoma (GBM) is one of the most frequent and lethal forms of brain tumors. In spite of the advances in therapies, the survival of patients is generally inferior to 1 year [1]. Different anti-angiogenic approaches with variable efficiency were developed Among these a number of peptide mimetics based on sequences derived from Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, have been tested [2]. ABT-510, a TSP-1 mimetic drug, designed with TSRs as base, displayed anti-angiogenic properties in a phase 1 clinical trial in newly diagnosed glioblastoma [4, 5]. This peptide inhibited tumor growth in vivo and induced endothelial cells apoptosis in vitro [6]. The comparison of the properties of NX with TSP-1 in tumor angiogenesis demonstrates that the NX affords a new type of anti-angiogenic agents, displaying distinct properties from TSP-1 and could be of interest for the development of therapeutic strategies to target highly vascularized tumors such as glioblastoma
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
