Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells

Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells
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DOI:
10.1016/j.bbrc.2012.02.054
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发表时间:
2012-03-16
影响因子:
3.1
通讯作者:
Morimoto, Chikao
Morimoto, Chikao
中科院分区:
生物学4区
文献类型:
--
作者:
Yamazaki, Hiroto;Naito, Motohiko;Morimoto, Chikao

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恶性间皮瘤(MM)是一种与石棉有关的恶性肿瘤,其特点是生长迅速,预后差。在我们以前的研究中,我们已经证明了几种癌症干细胞(CSC)标志物与MM细胞中的CSC特性相关。在这些标记物中,我们集中在两个:CD 29,共同的CSC标记物,和CD 26,额外的CSC标记物。我们进一步分析了CD 24和CD 26阳性MM细胞的CSC特性。我们建立了RNAi敲低细胞,发现这些标记物与体外化疗耐药性、增殖和侵袭潜力显著相关。有趣的是,虽然Meso-1细胞表达CD 24和CD 26两者,但这两种标志物中的每一种的存在与不同的CSC性质相关。此外,通过微阵列分析探索这些标记物的下游信号传导,其显示它们的表达与几个癌症相关基因相关。此外,表皮生长因子刺激的ERR的磷酸化显著受CD 26的表达影响,但不受CD 24的影响。这些结果表明,CD 24和CD 26差异调节CSC潜力的MM,并可能是有前途的目标CSC为导向的治疗。(C)2012 Elsevier Inc. All rights reserved.
Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSC properties in MM cells. Among these markers, we focused on two: CD29, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERR by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy. (C) 2012 Elsevier Inc. All rights reserved.