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Bmi-1 promotes glioma angiogenesis by activating NF-κB signaling.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (1), pp. e55527. Date of Electronic Publication: 2013 Jan 31. - Publication Year :
- 2013
-
Abstract
- Angiogenesis in glioma is associated with the poor prognosis of the disease and closely correlates with the highly invasive phenotype of glioma cells, which represents the most challenging impediment against the currently glioma treatments. Bmi-1, an onco-protein, has been implicated in the progression of various human cancers, including gliomas, whereas its role in glioma angiogenesis remains unclear. Our current study examined the effects of Bmi-1 on glioma angiogenesis in vitro as well as in vivo. We found that overexpression of Bmi-1 enhanced, whereas knockdown of Bmi-1 diminished, the capability of glioma cells to induce tubule formation and migration of endothelial cells and neovascularization in chicken chorioallantoic membrane. In vivo, Bmi-1 overexpression and knockdown, respectively, promoted and inhibited angiogenesis in orthotopically transplanted human gliomas. Furthermore, NF-κB activity and VEGF-C expression was induced by Bmi-1 overexpression, whereas Bmi-1 knockdown attenuated NF-κB signaling and decreased VEGF-C expression. Additionally suppression of NF-κB activity using a specific chemical inhibitor abrogated the NF-κB activation and the pro-angiogenic activities of glioma cells. Together, our data suggest that Bmi-1 plays an important role in glioma angiogenesis and therefore could represent a potential target for anti-angiogenic therapy against the disease.
- Subjects :
- Animals
Cell Line, Tumor
Chick Embryo
Enzyme Activation
Gene Expression
Gene Silencing
Humans
Mice
RNA Interference
Transplantation, Heterologous
Vascular Endothelial Growth Factor C genetics
Vascular Endothelial Growth Factor C metabolism
Glioma genetics
Glioma metabolism
NF-kappa B metabolism
Neovascularization, Pathologic genetics
Polycomb Repressive Complex 1 genetics
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23383216
- Full Text :
- https://doi.org/10.1371/journal.pone.0055527