Normal and neoplastic urothelial stem cells: getting to the root of the problem.
Normal and neoplastic urothelial stem cells: getting to the root of the problem.
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DOI：
10.1038/nrurol.2012.142
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发表时间：
2012-10
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影响因子：
--
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中科院分区：
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--
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大多数上皮组织含有自我更新的干细胞，这些干细胞成熟为分化潜力越来越有限的下游后代。从这种层级组织的上皮组织中产生的癌症保留了细胞分化的特征也就不足为奇了。越来越多的证据表明，膀胱的尿路上皮是一个有层次结构的组织，含有组织特异性干细胞，对正常的内稳态和损伤反应都是重要的。从膀胱癌组织中分离出的肿瘤干细胞(CSCs；也称为肿瘤起始细胞)的表型和功能特性已被详细研究。尿路上皮癌干细胞不是通过“一刀切”的方法分离出来的；相反，各种细胞表面标记组合(可能反映细胞起源)被用来从不同分化亚型的尿路上皮癌中分离出CSCs。其他CSC标志物，包括细胞角蛋白14(CK14)、乙醛脱氢酶1家族成员A1(ALDH1A1)和肿瘤蛋白63(P63)，已显示出对尿路上皮癌的预后价值。参与正常干细胞自我更新和分化的信号通路与不同亚型的尿路上皮癌的恶变有关。原始CK14+细胞的早期扩张--由STAT3等遗传途径驱动--可导致原位癌的发展，而富含CSC的尿路上皮癌与不良的临床预后有关。鉴于膀胱CSCs被认为是恶性的根源和尿路上皮癌发生和发展的驱动力，这些细胞是抗癌治疗的理想靶点。
Most epithelial tissues contain self-renewing stem cells that mature into downstream progenies with increasingly limited differentiation potential. It is not surprising that cancers arising from such hierarchically organized epithelial tissues retain features of cellular differentiation. Accumulating evidence suggests that the urothelium of the urinary bladder is a hierarchically organized tissue, containing tissue-specific stem cells that are important for both normal homeostasis and injury response. The phenotypic and functional properties of cancer stem cells (CSCs; also known as tumour-initiating cells) from bladder cancer tissue have been studied in detail. Urothelial CSCs are not isolated by a ‘one-marker-fits-all’ approach; instead, various cell surface marker combinations (possibly reflecting the cell-of-origin) are used to isolate CSCs from distinct differentiation subtypes of urothelial carcinomas. Additional CSC markers, including cytokeratin 14 (CK14), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and tumour protein 63 (p63), have revealed prognostic value for urothelial carcinomas. Signalling pathways involved in normal stem cell self-renewal and differentiation are implicated in the malignant transformation of different subsets of urothelial carcinomas. Early expansion of primitive CK14+ cells—driven by genetic pathways such as STAT3—can lead to the development of carcinoma in situ, and CSC-enriched urothelial carcinomas are associated with poor clinical outcomes. Given that bladder CSCs are the proposed root of malignancy and drivers of cancer initiation and progression for urothelial carcinomas, these cells are ideal targets for anticancer therapies.
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DOI：
10.1073/pnas.89.7.2804
发表时间：
1992-04-01
影响因子：
11.1
作者：
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通讯作者：
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DOI：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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影响因子：
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作者：
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