Abstract
Abstract Glioblastoma remains the deadliest form of brain tumors. The poor prognosis of glioblastoma patients is associated with a high rate of relapse after therapy. It has been suggested that the presence of cancer stem cells, which are relatively resistant to radiation and chemotherapy, may play a significant role in the recurrence of brain tumor. Understanding the biological property of brain tumor stem cells is important to develop effective therapeutic strategies for glioblastoma. In vitro, glioblastoma stem cells cultured in serum-free medium form self-renewing neurospheres, express the neural stem marker CD133, and are highly tumorigenic. On the other hand, in the presence of fetal bovine serum (FBS), the glioblastoma stem cells tend to undergo differentiation. In this study we used glioblastoma stem cells, NSC11 and NSC23, previously isolated from glioblastoma patients and expressed stem cell markers CD133 and SOX 2, to explore their bioenergetics by monitoring the oxygen consumption as an indication of mitochondrial respiration cultured in serum-free medium in comparison with that incubated in medium containing 5% FBS. We found that NSC11 and NSC23 stem cells exhibited low mitochondrial respiration when cultured in stem cell medium without serum. Upon exposure to 5% fetal bovine serum, mitochondrial respiration increased significantly. Moreover we assessed the protein expression of the mitochondrial respiratory complex (MRC) components in the cells cultured in serum-free medium in comparison with that in medium containing 5% FBS for various lengths of time by western blotting analysis. We observed a marked up-regulation of the protein subunits of MRC complexes I and IV in glioblastoma stem cells when they were exposed to FBS. Analysis of the mRNA expression levels for the mitochondrial DNA-encoded MRC components showed an increase in the expression of these genes, indicating an increase in the mitochondria biogenesis upon the FBS exposure. Based on these preliminary findings, we postulate that maintaining low mitochondrial respiration may be important to maintain the stemness of the glioblastoma stem cells, while the activation of the respiration may promote stem cell differentiation and affect their tumorgenecity. Further studies are required to elucidate the detail molecular pathways governing glioblastoma stem cell self-renewal and differentiation and the mechanistic link to mitochondrial function. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3314. doi:10.1158/1538-7445.AM2011-3314
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