Epithelial Mesenchymal Transition Traits in Human Breast Cancer Cell Lines Parallel the CD44hi/CD24lo/- Stem Cell Phenotype in Human Breast Cancer
Epithelial Mesenchymal Transition Traits in Human Breast Cancer Cell Lines Parallel the CD44hi/CD24lo/- Stem Cell Phenotype in Human Breast Cancer
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DOI：
10.1007/s10911-010-9175-z
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发表时间：
2010-06-01
影响因子：
2.5
通讯作者：
Thompson, Erik W.
中科院分区：
文献类型：
--
作者：
Blick, Tony;Hugo, Honor;Thompson, Erik W.
我们在此回顾了最近出现的上皮间质转化 (EMT) 和乳腺癌干细胞 (BCSC) 之间的关系，并提供了对人类乳腺癌细胞系已发表数据的分析，支持它们作为 EMT/BCSC 状态模型的实用性。这些细胞系的全基因组转录分析证实存在具有间充质倾向和增强侵袭特性的亚组（“Basal B”/间充质），与具有主要管腔（“Luminal”）或混合基底/管腔（“Basal A”）特征的亚组不同（Neve等人，Cancer Cell，2006）。文献衍生的 EMT 基因特征显示，Basal B 细胞系亚组内存在特异性富集，这与其各种 EMT 转录驱动因子的过度表达相一致。发现基底 B 细胞系与 BCSC 类似，为 CD44（高）CD24（低）。此外，据 Shipitsin 等人报道，区分 Basal B 与 Basal A 和 Luminal 细胞系（Basal B 鉴别器）的基因产物与定义从临床材料中分离的 BCSC 的基因产物非常一致。 （癌细胞，2007）。 CD24 mRNA 水平在不同的 Basal B 细胞系中存在差异，与其他 Basal B 鉴别器相关。许多与基底 B 细胞系中 CD24 状态相关的基因产物也在分离的 BCSC 中差异表达。这些发现证实并扩展了基底 B 细胞系 EMT 细胞产物的重要性，并说明了分析这些细胞系寻找可能改善乳腺癌结果的新线索的价值。基底 B 细胞系特异的基因产物可作为检测、定量和分析 BCSC/EMT 属性的工具。
We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44(high)CD24(low). Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.