Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.
Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.
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DOI：
10.1016/j.stemcr.2013.11.009
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发表时间：
2014-01-14
影响因子：
5.9
通讯作者：
Wicha MS
中科院分区：
文献类型：
--
作者：
Liu S;Cong Y;Wang D;Sun Y;Deng L;Liu Y;Martin-Trevino R;Shang L;McDermott SP;Landis MD;Hong S;Adams A;D'Angelo R;Ginestier C;Charafe-Jauffret E;Clouthier SG;Birnbaum D;Wong ST;Zhan M;Chang JC;Wicha MS
先前的研究表明，乳腺癌干细胞（BCSC）介导转移，对放疗和化疗具有抗性，并有助于复发。虽然已经描述了几种BCSC标记物，但尚不清楚这些标记物是否鉴定相同或独立的BCSC。在这里，我们发现BCSCs存在于不同的间充质样（上皮-间充质转化[EMT]）和上皮样（间充质-上皮转化[MET]）状态。以CD 24 − CD 44+为特征的间充质样BCSC主要是静止的，位于肿瘤浸润前沿，而上皮样BCSC表达醛脱氢酶（ALDH），是增殖性的，位于更中心的位置。间充质样和上皮样BCSC的基因表达谱在乳腺癌的不同分子亚型中非常相似，并且类似于在正常乳腺中发现的不同基底和管腔干细胞的基因表达谱。我们认为，BCSC的可塑性使它们能够在EMT和MET样状态之间转换，从而赋予这些细胞在转移部位的组织侵袭、传播和生长的能力。BCSC以EMT和MET状态存在，具有不同的标志物和基因表达谱来自不同亚型的乳腺癌的CSC表达共同的EMT/MET基因EMT和MET BCSC谱类似于正常的乳腺基底和腔干细胞BCSC显示可塑性，使它们能够在EMT和MET状态之间转换乳腺癌干细胞（BCSC）被认为介导转移和对放疗和化疗的抗性。在这里，刘等人。显示BCSC以不同的间充质样（CD 24 − CD 44+）和上皮样（ALDH+）状态存在，具有不同的增殖和侵袭能力，表明靶向替代CSC状态可能具有临床重要性。
Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24−CD44+ are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites. BCSCs exist in EMT and MET states with distinct marker and gene-expression profiles CSCs from different subtypes of breast cancer express common EMT/MET genes EMT and MET BCSC profiles resemble normal mammary basal and luminal stem cells BCSCs display plasticity that enables them to transition between EMT and MET states Breast cancer stem cells (BCSCs) are thought to mediate metastasis and resistance to radiation and chemotherapy. Here, Liu et al. show that BCSCs exist in distinct mesenchymal-like (CD24−CD44+) and epithelial-like (ALDH+) states with different proliferative and invasive capacities, suggesting it may be clinically important to target alternative CSC states.