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从小鼠胚胎干细胞诱导生成癌症干细胞。

Cancer stem cell induction from mouse embryonic stem cells.

作者信息

Seno Akimasa, Murakami Chikae, El-Aarag Bishoy, Iwasaki Yoshiaki, Ohara Toshiaki, Seno Masaharu

机构信息

Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan.

Okayama University Research Laboratory for Stem Cell Engineering in Detroit, Integrative Biosciences Center, Wayne State University, Detroit, MI 48202, USA.

出版信息

Oncol Lett. 2019 Sep;18(3):2756-2762. doi: 10.3892/ol.2019.10614. Epub 2019 Jul 15.

Abstract

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.

摘要

尽管癌症通常通过手术切除,并采用化疗和/或放射疗法进行治疗,但由于存在如癌症干细胞(CSCs)等耐药残留细胞,癌症在治疗后往往会复发。癌症干细胞具有自我更新、多能性和致瘤性等特性,是癌症彻底治疗的有前景的治疗靶点;然而,癌症组织中癌症干细胞的数量通常过少,难以进行全面研究。我们之前曾报道,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(iPSCs)中建立癌症干细胞。在本研究中,观察到小鼠胚胎干细胞(mESCs)可转化为癌症干细胞(mES-CSCs)。这表明癌症干细胞的诱导并非仅发生在体细胞基因编辑之后,而且癌细胞的条件培养基可能含有能够诱导癌症干细胞的因子。因此,不仅诱导多能干细胞,小鼠胚胎干细胞也被证明能够作为干细胞多能性的一种潜能产生癌症干细胞,这表明向癌症干细胞的转化并非诱导多能干细胞所特有。所得的小鼠胚胎干细胞来源的癌症干细胞对于生成组织特异性癌症也将是有用的,这些自然发生的癌症不仅有助于药物筛选,还可进行进一步研究以揭示癌症机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcef/6676632/d75c12f78891/ol-18-03-2756-g00.jpg

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