CD133 Expression Is Not Synonymous to Immunoreactivity for AC133 and Fluctuates throughout the Cell Cycle in Glioma Stem-Like Cells.

CD133 Expression Is Not Synonymous to Immunoreactivity for AC133 and Fluctuates throughout the Cell Cycle in Glioma Stem-Like Cells.
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DOI:
10.1371/journal.pone.0130519
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Kim EL
Kim EL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barrantes-Freer A;Renovanz M;Eich M;Braukmann A;Sprang B;Spirin P;Pardo LA;Giese A;Kim EL

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一种跨膜蛋白CD133被认为是干细胞样胶质瘤细胞的标志物和恶性脑肿瘤治疗反应的预测因子。CD133表达通常通过使用位于膜结合CD133的细胞外结构域之一的AC133表位特异性抗体来评估。关于AC133表位作为鉴别干细胞样胶质瘤细胞和预测胶质瘤细胞恶性程度的标志物的意义,有相互矛盾的证据。关于CD133/AC133在胶质瘤中的作用的不同研究结果差异的原因尚不清楚。关于CD133/AC133争议的一个可能来源是人们普遍认为AC133表位的表达模式线性地反映了CD133蛋白的表达模式。因此,AC133评估的读数通常根据CD133蛋白来解释。本研究的目的是确定抗ac133抗体获得的读数是否以及在多大程度上对应于干细胞样胶质瘤细胞中CD133蛋白的表达水平。我们的研究首次揭示了在胶质瘤细胞表面表达的CD133对AC133的免疫反应性较差。此外,我们提供的证据表明,CD133在胶质瘤细胞表面的占用水平在细胞周期中波动。我们的研究结果为关于CD133/AC133在人类胶质瘤中的生物学和临床意义的许多不一致提供了新的解释,并呼吁在解释胶质瘤细胞中AC133表位的缺乏或存在时要谨慎。
A transmembrane protein CD133 has been implicated as a marker of stem-like glioma cells and predictor for therapeutic response in malignant brain tumours. CD133 expression is commonly evaluated by using antibodies specific for the AC133 epitope located in one of the extracellular domains of membrane-bound CD133. There is conflicting evidence regarding the significance of the AC133 epitope as a marker for identifying stem-like glioma cells and predicting the degree of malignancy in glioma cells. The reasons for discrepant results between different studies addressing the role of CD133/AC133 in gliomas are unclear. A possible source for controversies about CD133/AC133 is the widespread assumption that expression patterns of the AC133 epitope reflect linearly those of the CD133 protein. Consequently, the readouts from AC133 assessments are often interpreted in terms of the CD133 protein. The purpose of this study is to determine whether and to what extent do the readouts obtained with anti-AC133 antibody correspond to the level of CD133 protein expressed in stem-like glioma cells. Our study reveals for the first time that CD133 expressed on the surface of glioma cells is poorly immunoreactive for AC133. Furthermore, we provide evidence that the level of CD133 occupancy on the surface of glioma cells fluctuates during the cell cycle. Our results offer a new explanation for numerous inconsistencies regarding the biological and clinical significance of CD133/AC133 in human gliomas and call for caution in interpreting the lack or presence of AC133 epitope in glioma cells.
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