Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state
Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state
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DOI：
10.1073/pnas.1102454108
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发表时间：
2011-05-10
影响因子：
11.1
通讯作者：
Weinberg, Robert A.
中科院分区：
文献类型：
--
作者：
Chaffer, Christine L.;Brueckmann, Ines;Weinberg, Robert A.
当前的干细胞生物学模型假定，正常和肿瘤性干细胞位于层级结构的顶端，并以单向方式分化为非干细胞后代。在此，我们鉴定出一种基底样人类乳腺上皮细胞亚群，它背离了这一假定，会自发地去分化为干细胞样细胞。此外，致癌转化增强了这种自发转化，使得非干细胞癌细胞在体外和体内产生癌症干细胞（CSC）样细胞。我们进一步表明，正常起源细胞的分化状态是转化后行为的一个重要决定因素。这些发现表明，正常细胞和CSC样细胞可以从更分化的细胞类型中重新产生，并且乳腺干细胞生物学的层级模型应包含干细胞和非干细胞区间的双向相互转化。所观察到的可塑性可能允许在不进行基因操作的情况下获得患者特异性的成体干细胞，并且对根除癌症的治疗策略具有重要意义。
Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectionalmanner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer.