CD133 is a marker of bioenergetic stress in human glioma.
CD133 is a marker of bioenergetic stress in human glioma.
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DOI：
10.1371/journal.pone.0003655
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Gillespie GY
中科院分区：
文献类型：
--
作者：
Griguer CE;Oliva CR;Gobin E;Marcorelles P;Benos DJ;Lancaster JR Jr;Gillespie GY
线粒体功能障碍和低氧微环境是癌细胞生物学的特征。近年来，许多研究都集中在利用CD133的表达来分离脑肿瘤干细胞。在这项研究中，我们研究了CD133的表达是否受到影响人脑胶质瘤细胞线粒体功能的生物能量应激的调节。首先，我们确定了低氧诱导了CD133表达的可逆上调。其次，通过药物抑制电子传输链(ETC)而导致的线粒体功能障碍导致CD133表达上调，这与线粒体膜电位的变化呈负相关。第三，稳定的线粒体DNA缺失的胶质瘤细胞CD133的表达显著而稳定地增加。这些胶质瘤细胞被称为Rho 0或ρ0，其特征是具有夸张的、解偶联的糖酵解表型，并通过许多细胞传代结构性和稳定地上调CD133。此外，这些ρ-0细胞在无血清培养中具有形成“肿瘤球体”的能力，CD133和神经前体细胞标记物Nestin呈阳性反应。在分化条件下，ρ0细胞表现出多谱系特性。通过将亲本线粒体转移到ρ-0细胞，获得稳定的跨线粒体“胞质”克隆，证明了CD133表达的可逆性。这项研究为环境条件(缺氧)和线粒体功能障碍(遗传和化学)对CD133的调节提供了一种新的机制见解。考虑到这些新发现，CD133是脑瘤干细胞标记物的概念可能需要修改。
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 ρ0, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these ρ0 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, ρ0 cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to ρ0 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.
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影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
影响因子：
3.9
作者：
Griguer, Corinne E.;Oliva, Claudia R.;Marcorelles, Pascale
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Marcorelles, Pascale
影响因子：
5
作者：
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通讯作者：
Pollack, IF
影响因子：
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作者：
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通讯作者：
Knisely, JPS
影响因子：
4.8
作者：
Bouzier, AK;Goodwin, R;Merle, M
通讯作者：
Merle, M