Cancer stem cell induction from mouse embryonic stem cells

Cancer stem cell induction from mouse embryonic stem cells
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DOI:
10.3892/ol.2019.10614
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发表时间:
2019-09-01
期刊:
影响因子:
2.9
通讯作者:
Seno, Masaharu
Seno, Masaharu
中科院分区:
医学4区
文献类型:
--
作者:
Seno, Akimasa;Murakami, Chikae;Seno, Masaharu

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虽然癌症通常通过手术切除并通过化疗和/或放射疗法治疗,但由于存在抗性残留细胞如癌症干细胞(CSC),它们通常在治疗后复发。CSC的特征在于其自我更新、多能性和致瘤性,并且是用于癌症的完全治疗的有希望的治疗靶点;然而,癌症组织中CSC的数量通常太少而不能充分研究。我们以前曾报道过,在癌细胞培养过程中,使用条件培养基可以从诱导多能干细胞(iPSC)中建立CSC。在本研究中,观察到小鼠胚胎干细胞(mESC)转化为CSC(mES-CSC)。这表明CSC诱导并不完全发生在体细胞中的基因编辑之后,并且来自癌细胞的条件培养基可能含有可以诱导CSC的因子。因此,不仅iPSC而且mESC都被证明能够产生CSC作为干细胞多能性的潜力之一,这表明向CSC的转化不是iPSC所特有的。所得到的mES-CSC也可用于产生组织特异性癌症,并且这些天然存在的癌症可以有助于药物筛选,但也可以进行进一步的研究以揭示癌症机制。
Although cancers are often removed by surgery and treated by chemotherapy and/or radiation therapies, they often reoccur following treatment due to the presence of resistant residual cells such as cancer stem cells (CSCs). CSCs are characterized by their self-renewal, pluripotency, and tumorigenicity properties, and are promising therapeutic targets for the complete therapy of cancers; however, the number of CSCs in cancer tissue is typically too small to investigate fully. We have previously reported that CSCs could be established from induced pluripotent stem cells (iPSCs) using a conditioned medium during cancer cell culture. In the present study, mouse embryonic stem cells (mESCs) were observed to be converted to CSCs (mES-CSCs). This demonstrated that CSC induction does not exclusively occur following gene editing in somatic cells, and that conditioned medium from cancer cells may contain factors that can induce CSCs. Therefore, not only iPSCs but also mESCs, were demonstrated to be able to produce CSCs as one of the potentials of pluripotency of stem cells, suggesting that the conversion to CSCs is not specific to iPSCs. The resultant mES-CSCs would be also useful to generate tissue specific cancers and these naturally occurring cancers can contribute to drug screenings, but also undergo further investigation in order to reveal cancer mechanisms.