Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative
Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative
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DOI：
10.1158/0008-5472.can-11-1059
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发表时间：
2011-08-01
期刊：
影响因子：
11.2
通讯作者：
Mackenzie, Ian C.
中科院分区：
文献类型：
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作者：
Biddle, Adrian;Liang, Xiao;Mackenzie, Ian C.
上皮向间充质转化(EMT)是肿瘤侵袭和转移的重要驱动力，可导致许多肿瘤死亡。维持和启动肿瘤的肿瘤干细胞(CSC)也参与了肿瘤的侵袭和转移，但EMT是否是CSC功能的重要贡献者尚不清楚。在这项研究中，我们调查了鳞状细胞癌(SCC)中是否存在接受EMT的CSCs群体(EMT CSCs)。我们还确定了是否也存在保留上皮特征的单独的CSCs(非EMT CSCs)。我们的研究表明，SCC中的自我更新的CSCs包括两种不同的生物学表型。一种表型为CD44(High)ESA(High)，为增殖性并保留上皮特征(Non-EMT CSCs)，另一种表型为CD44(High)ESA(Low)，具有EMT CSCs的移行和间质特征。我们发现，非EMT和EMT CSCs可以改变其上皮或间充质特性，以重建CSCs特有的细胞异质性。然而，EMT CSCs转换为非EMT特性的能力仅限于ALDH1(+)的细胞，这意味着只有ALDH1(+)的EMT细胞才有能力种植新的上皮性肿瘤。综上所述，我们的发现突出了两种不同的CSC表型的识别，并建议有必要定义能够根除这两种变异的治疗靶点，以实现有效的SCC治疗。癌症资源；71(15)；5317-26。(C)2011年AACR。
Epithelial-to-mesenchymal transition (EMT) is an important driver of tumor invasion and metastasis, which causes many cancer deaths. Cancer stem cells (CSC) that maintain and initiate tumors have also been implicated in invasion and metastasis, but whether EMT is an important contributor to CSC function is unclear. In this study, we investigated whether a population of CSCs that have undergone EMT (EMT CSCs) exists in squamous cell carcinoma (SCC). We also determined whether a separate population of CSCs that retain epithelial characteristics (non-EMT CSCs) is also present. Our studies revealed that self-renewing CSCs in SCC include two biologically-distinct phenotypes. One phenotype, termed CD44(high)ESA(high), was proliferative and retained epithelial characteristics (non-EMT CSCs), whereas the other phenotype, termed CD44(high)ESA(low), was migratory and had mesenchymal traits characteristic of EMT CSCs. We found that non-EMT and EMT CSCs could switch their epithelial or mesenchymal traits to reconstitute the cellular heterogeneity which was characteristic of CSCs. However, the ability of EMT CSCs to switch to non-EMT character was restricted to cells that were also ALDH1(+), implying that only ALDH1(+) EMT cells had the ability to seed a new epithelial tumor. Taken together, our findings highlight the identification of two distinct CSC phenotypes and suggest a need to define therapeutic targets that can eradicate both of these variants to achieve effective SCC treatment. Cancer Res; 71(15); 5317-26. (C) 2011 AACR.