Method to Convert Stem Cells into Cancer Stem Cells

Method to Convert Stem Cells into Cancer Stem Cells
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DOI:
10.3390/mps2030071
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发表时间:
2019-09-01
影响因子:
2.4
通讯作者:
Seno, Masahura
Seno, Masahura
中科院分区:
其他
文献类型:
--
作者:
Afify, Said M.;Chen, Ling;Seno, Masahura

文献摘要

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癌症干细胞(CSC)假说表明,肿瘤是由一小群具有干细胞特性的细胞维持的。CSC已在大多数肿瘤中被鉴定,并且负责不同癌症的起始、复发和抗性。体外CSC模型将有助于重新审视癌症发展的机制,以及肿瘤微环境和癌症和转移的异质性。我们的小组最近描述了从诱导多能干细胞(iPSC)中产生CSC,iPSC是从正常细胞和/或胚胎干细胞(ESC)重新编程的。这一程序将提高对癌症发生所涉及的基本生态位的理解。如果确定了这种癌症诱导生态位的组成,将让我们知道正常细胞如何在体内转化为恶性细胞,以及如何反过来实现癌症预防。此外,一旦发育,CSC表现出分化成内皮细胞、癌症相关成纤维细胞和建立CSC生态位的其他表型的能力。这些将是开发新的癌症治疗方法的良好材料。在该方案中,我们描述了如何处理小鼠iPSCs/ESC以及如何选择开始转化为CSC的关键时间。该CSC生成方案对于理解CSC在癌症发生和进展中的作用至关重要。
The cancer stem cell (CSC) hypothesis suggests that tumors are sustained exclusively by a small population of the cells with stem cell properties. CSCs have been identified in most tumors and are responsible for the initiation, recurrence, and resistance of different cancers. In vitro CSC models will be of great help in revisiting the mechanism of cancer development, as well as the tumor microenvironment and the heterogeneity of cancer and metastasis. Our group recently described the generation of CSCs from induced pluripotent stem cells (iPSCs), which were reprogrammed from normal cells, and/or embryonic stem cells (ESCs). This procedure will improve the understanding of the essential niche involved in cancer initiation. The composition of this cancer-inducing niche, if identified, will let us know how normal cells convert to malignant in the body and how, in turn, cancer prevention could be achieved. Further, once developed, CSCs demonstrate the ability to differentiate into endothelial cells, cancer-associated fibroblasts, and other phenotypes establishing the CSC niche. These will be good materials for developing novel cancer treatments. In this protocol, we describe how to handle mouse iPSCs/ESCs and how to choose the critical time for starting the conversion into CSCs. This CSC generation protocol is essential for understanding the role of CSC in cancer initiation and progress.