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- Title
Metabolic activation of mitochondria in glioma stem cells promotes cancer development through a reactive oxygen species-mediated mechanism.
- Authors
Shuqiang Yuan; Yunxin Lu; Jing Yang; Gang Chen; Sangbae Kim; Li Feng; Ogasawara, Marcia; Hammoudi, Naima; Weiqin Lu; Hui Zhang; Jinyun Liu; Colman, Howard; Ju-Seog Lee; Xiao-Nan Li; Rui-hua Xu; Peng Huang; Feng Wang
- Abstract
Introduction: Cancer stem cells (CSCs) possess characteristics associated with normal stem cells, specifically the abilities to renew themselves and to give rise to all cell types (differentiation). It is assumed that induction of differentiation in CSCs would reduce their ability to form tumors. What triggers CSC differentiation and the role of "differentiation" in tumorigenesis remain elusive. Methods: Glioma stem cell (GSC) lines and subcutaneous as well as orthotopic xenografts established from fresh surgical specimens of glioblastoma multiforme were used. Results: Exposure of GSCs to serum activates mitochondrial respiration and causes an increase in mitochondrial reactive oxygen species (ROS) as well as oxidative stress responses, leading to the appearance of differentiation morphology and a deceased expression of CSC markers. Chemical perturbation of the mitochondrial electron transport chain causes ROS increase and further downregulation of stem cell markers, while antioxidant N-acetylcysteine reduces ROS and suppresses the differentiation of GSCs. Surprisingly, the serum-induced differentiated GSCs exhibit greater ability to form tumor in both orthotopic and subcutaneous xenograft models, which can be suppressed by N-acetyl-cysteine. Mitochondrial ROS from the serum-stimulated cells triggered the activation of nuclear factor-kappa-B (NFκB) pathway, which is a potential mechanism for the promotion of tumorigenesis. Conclusion: This study suggests that ROS generated from active mitochondrial respiration in the presence of serum is critical in CSCs activation, which promotes tumor development in vivo.
- Subjects
MITOCHONDRIA; GLIOMAS; CANCER stem cells; CANCER invasiveness; NEOPLASTIC cell transformation
- Publication
Stem Cell Research & Therapy, 2015, p1
- ISSN
1757-6512
- Publication type
Article
- DOI
10.1186/s13287-015-0174-2