Targeting of cancer stem cells by differentiation therapy
Targeting of cancer stem cells by differentiation therapy
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DOI：
10.1111/cas.14504
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发表时间：
2020-06-22
期刊：
影响因子：
5.7
通讯作者：
Saya, Hideyuki
中科院分区：
文献类型：
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作者：
Arima, Yoshimi;Nobusue, Hiroyuki;Saya, Hideyuki
化疗耐药是肿瘤干细胞(CSCs)的一个标志。为了开发针对CSCs的新的治疗策略，我们通过将c-Myc基因导入来自Ink4a/ArfKO小鼠的骨髓基质细胞来建立骨肉瘤起始(OSI)细胞。这些OSI细胞包括具有高致瘤活性的双能定向细胞(类似于骨软骨前体细胞)以及具有低致瘤性的三能细胞(类似于间充质干细胞)。我们最近发现，三能OSI细胞对化疗药物具有高度的耐药性，这些细胞中肌动蛋白细胞骨架的解聚诱导它们的终末脂肪细胞分化，并抑制它们的致瘤性。我们在此综述了骨肉瘤中与终末脂肪细胞分化相关的肌动蛋白细胞骨架动力学的调节，并讨论了通过诱导其分化来针对化疗耐药肿瘤干细胞的新的治疗策略的前景。
Chemoresistance is a hallmark of cancer stem cells (CSCs). To develop novel therapeutic strategies that target CSCs, we established osteosarcoma-initiating (OSi) cells by introducing the c-Myc gene into bone marrow stromal cells derived fromInk4a/ArfKO mice. These OSi cells include bipotent committed cells (similar to osteochondral progenitor cells) with a high tumorigenic activity as well as tripotent cells (similar to mesenchymal stem cells) of low tumorigenicity. We recently showed that the tripotent OSi cells are highly resistant to chemotherapeutic agents, and that depolymerization of the actin cytoskeleton in these cells induces their terminal adipocyte differentiation and suppresses their tumorigenicity. We here provide an overview of modulation of actin cytoskeleton dynamics associated with terminal adipocyte differentiation in osteosarcoma as well as discuss the prospects for new therapeutic strategies that target chemoresistant CSCs by inducing their differentiation.