Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer
Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer
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DOI：
10.1007/s10911-010-9173-1
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发表时间：
2010-06-01
影响因子：
2.5
通讯作者：
Rosen, Jeffrey M.
中科院分区：
文献类型：
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作者：
Creighton, Chad J.;Chang, Jenny C.;Rosen, Jeffrey M.
越来越多的证据支持这样一种假说：大多数肿瘤包含一个细胞亚群，在此称为肿瘤起始细胞（TICs），它们具有自我更新以及再生肿瘤内所有细胞类型的能力。在常规治疗后，乳腺癌患者体内的TICs会富集，这表明它们具有内在的治疗抗性。来自不同研究的两个独立得出的TICs基因转录“特征”表明，在最近确定的乳腺癌“低紧密连接蛋白”内在分子亚型中TICs富集。这些细胞的特征是与上皮 - 间质转化（EMT）相关的标志物高表达，这表明低紧密连接蛋白细胞可能比其他乳腺癌源自更不成熟的干细胞或祖细胞。EMT是一个细胞获得分子改变的过程，这种改变促进细胞 - 细胞黏附相互作用和连接功能失调，以及形成更纺锤状的形态。这些过程可能促进癌细胞进展以及侵入周围微环境。在永生化的人乳腺上皮细胞中诱导EMT会导致形成乳腺球的能力增强，以及干细胞和TIC标志物的表达，这表明EMT和TIC特性的获得之间可能存在直接联系。除了针对肿瘤主体的常规化疗和放疗外，针对TIC亚群中与发育和EMT相关的特定分子途径（如Notch、Wnt和TGF），最终可能为治疗乳腺癌提供更有效的策略。在此，我们综述了EMT参与乳腺癌TICs的最新证据，重点关注临床研究。
There is increasing support for the hypothesis that most tumors contain a subpopulation of cells, referred to here as tumor initiating cells (TICs), with the ability to self-renew and to regenerate all the cell types within the tumor. TICs are enriched in breast cancer patients after common treatments, indicating their intrinsic therapeutic resistance. Two independently-derived gene transcription "signatures" of TICs from different studies indicate enrichment of TICs within the recently-identified "claudin-low" intrinsic molecular subtype of breast cancer. These are characterized by high expression of markers associated with epithelial-mesenchymal transition (EMT), suggesting that claudin-low cells may arise from more immature stem or progenitor cells than other breast cancers. EMT is a process by which cells acquire molecular alterations that facilitate dysfunctional cell-cell adhesive interactions and junctions, as well as a more spindle-shaped morphology. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Induction of EMT in immortalized human mammary epithelial cells results in an increased ability to form mammospheres, and in the expression of stem cell and TIC markers, suggesting that there may be a direct link between the EMT and the gain of TIC properties. Targeting specific molecular pathways-such as Notch, Wnt, and TGF-associated with development and EMT in the TIC subpopulation, in addition to conventional chemo- and radiation therapies that target the bulk tumor, may ultimately provide a more effective strategy in treating breast cancer. Here, we review recent evidence of the involvement of EMT in breast cancer TICs, focusing on clinical studies.