SCO-spondin oligopeptide inhibits angiogenesis in glioblastoma
Romain Bibes1, Stéphane Gobron2, François Vincent1,3
1EA3842 Cellular Homeostasis and Diseases, University of Limoges, Faculty of Medicine, 87025 Limoges Cedex, France.
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.
Insights
The novel oligopeptide NX inhibits glioblastoma growth by blocking angiogenesis and endothelial cell migration. This molecule shows promise as a potential cancer therapy by targeting tumor vascularization.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Research
Background:
- Angiogenesis is crucial for glioblastoma (GBM) development and progression.
- Targeting angiogenesis offers a therapeutic strategy for GBM.
- SCO-spondin derived oligopeptide NX is investigated for anti-angiogenic properties.
Purpose of the Study:
- To evaluate the anti-angiogenic effects of the oligopeptide NX on human glioblastoma.
- To assess NX's impact on endothelial cell behavior and tumor vascularization.
- To explore NX as a potential therapeutic agent for GBM.
Main Methods:
- In vitro studies using human brain microvascular endothelial cells (HBMECs) and U87-MG glioblastoma cells.
- In vivo models including the chorioallantoic membrane (CAM) assay and glioblastoma xenografts.
- Analysis of apoptosis, proliferation, migration, angiogenic factor release, and gene expression.
Main Results:
- NX treatment reduced microvascular network formation, cell proliferation, vascularization, and tumor growth in CAM and xenograft models.
- NX impaired HBMECs migration and modulated angiogenic factor release from U87-MG cells.
- Gene expression profiling of NX-treated U87-MG cells on CAM revealed alterations in angiogenesis-related genes.
Conclusions:
- NX inhibits glioblastoma tumorigenesis by disrupting angiogenesis and endothelial cell migration.
- NX demonstrates significant anti-tumor and anti-angiogenic activity.
- NX is a promising candidate for future glioblastoma cancer therapies.
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