Journal article
CD133 Is a Marker of Bioenergetic Stress in Human Glioma
PloS one, Vol.3(11), pp.e3655-e3655
11/05/2008
DOI: 10.1371/journal.pone.0003655
PMCID: PMC2577012
PMID: 18985161
Abstract
Mitochondria dysfunction and hypoxic microenvironment are hallmarks of cancer cell biology. Recently, many studies have focused on isolation of brain cancer stem cells using CD133 expression. In this study, we investigated whether CD133 expression is regulated by bioenergetic stresses affecting mitochondrial functions in human glioma cells. First, we determined that hypoxia induced a reversible up-regulation of CD133 expression. Second, mitochondrial dysfunction through pharmacological inhibition of the Electron Transport Chain (ETC) produced an up-regulation of CD133 expression that was inversely correlated with changes in mitochondrial membrane potential. Third, generation of stable glioma cells depleted of mitochondrial DNA showed significant and stable increases in CD133 expression. These glioma cells, termed
rho
0
or ρ
0
, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these ρ
0
cells display the ability to form “tumor spheroids” in serumless medium and are positive for CD133 and the neural progenitor cell marker, nestin. Under differentiating conditions, ρ
0
cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to ρ
0
cells resulting in stable trans-mitochondrial “cybrid” clones. This study provides a novel mechanistic insight about the regulation of CD133 by environmental conditions (hypoxia) and mitochondrial dysfunction (genetic and chemical). Considering these new findings, the concept that CD133 is a marker of brain tumor stem cells may need to be revised.
Details
- Title: Subtitle
- CD133 Is a Marker of Bioenergetic Stress in Human Glioma
- Creators
- Corinne E GriguerClaudia R OlivaEric GobinPascale MarcorellesDale J BenosJack R LancasterG. Yancey Gillespie
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.3(11), pp.e3655-e3655
- DOI
- 10.1371/journal.pone.0003655
- PMID
- 18985161
- PMCID
- PMC2577012
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- CD133 and Bioenergetic Stress
- Language
- English
- Date published
- 11/05/2008
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047797202771
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