Key Laboratory of Protein Chemistry and Developmental Biology of Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan, China.
Cell Cycle. 2012 Jul 15;11(14):2691-8. doi: 10.4161/cc.21021.
Recent studies indicate that cancer stem cells (CSCs) exist in most hematological and solid tumors. CSCs are characterized by their ability to self-renew and their capacity to differentiate into the multitude of cells that comprise the tumor mass. Moreover, these cells have been shown to be intrinsically resistant to conventional anticancer therapies. Despite their fundamental role in cancer pathogenesis, the cellular origin of CSCs remains highly controversial. The aim of this study was to examine whether heterogeneous cancer cells can acquire stem cell-like properties in response to chemotherapy. We demonstrate that carboplatin can induce the self-renewal (spherogenesis) and pluripotency (Sox2 and Oct3/4 expression) of hepatocellular carcinoma (HCC) cells grown under stem cell culture conditions. Moreover, we show that non-CSC cells, obtained by side population flow cytometric sorting using Hoechst 33342, can acquire stem-like properties after exposure to carboplatin. Finally, we show that knockdown of Sox2 and Oct3/4 gene expression in HCC cells can reduce carboplatin-mediated increases in sphere formation and increase cellular sensitivity to chemotherapy. Taken together, our data indicate that bulk cancer cells may be an important source of CSCs during tumor development, and that targeting Sox2 and/or Oct3/4 may be a promising approach for targeting CSCs in clinical cancer treatment.
最近的研究表明，癌症干细胞（CSC）存在于大多数血液系统和实体肿瘤中。CSC 的特征是自我更新的能力，以及分化为构成肿瘤块的多种细胞的能力。此外，这些细胞已经被证明对传统的抗癌疗法具有内在的抗性。尽管它们在癌症发病机制中具有重要作用，但 CSC 的细胞起源仍然存在很大争议。本研究旨在探讨化疗是否能使异质癌细胞获得类似干细胞的特性。我们证明，顺铂可以诱导在干细胞培养条件下生长的肝细胞癌（HCC）细胞的自我更新（球体形成）和多能性（Sox2 和 Oct3/4 表达）。此外，我们还表明，通过 Hoechst 33342 侧向群体流式细胞术分选获得的非 CSC 细胞，在暴露于顺铂后可以获得类似干细胞的特性。最后，我们表明，在 HCC 细胞中敲低 Sox2 和 Oct3/4 基因表达可以减少顺铂介导的球体形成增加，并增加细胞对化疗的敏感性。总之，我们的数据表明，大量癌细胞可能是肿瘤发展过程中 CSC 的一个重要来源，靶向 Sox2 和/或 Oct3/4 可能是临床癌症治疗中靶向 CSC 的一种有前途的方法。
