Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan.
Int J Cancer. 2014 Jul 1;135(1):27-36. doi: 10.1002/ijc.28648. Epub 2013 Dec 9.
The self-renewal and differentiation properties of cancer stem cells (CSCs) are regulated and maintained by the CSC niche. However, the mechanism of this maintenance, especially the maintenance contributed by differentiated cancer cells, remains to be fully elucidated. Recently, we have established a model of CSCs, miPS-LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro cultured miPS-LLCcm cells were autonomously balanced with stem-like cells and differentiated cells including vascular endothelial cells. Under these conditions, the CSC properties appeared to be stable in the presence of the factor(s) secreted by the differentiated cells. The factor(s) activated Notch signaling and promoted self-renewal of CSCs. In addition, the secreted factor(s) appeared to regulate the differentiation lineage of CSCs. Our results indicate that the differentiated progenies of CSCs containing vascular endothelium play important roles for regulating the CSC's properties. Therefore, miPS-LLCcm cells create their own in vitro niche to maintain themselves in the hierarchy of differentiating CSCs.
癌症干细胞 (CSC) 的自我更新和分化特性受 CSC 生态位调控和维持。然而，这种维持的机制，特别是由分化的癌细胞贡献的维持机制，仍有待充分阐明。最近，我们从诱导多能干细胞 (miPSC) 中建立了一个 CSC 模型，miPS-LLCcm。在体外培养的 miPS-LLCcm 细胞中，干细胞样细胞和包括血管内皮细胞在内的分化细胞之间存在自主平衡。在这些条件下，CSC 特性在分化细胞分泌的因子存在下似乎保持稳定。该因子激活 Notch 信号通路并促进 CSC 的自我更新。此外，分泌的因子似乎调节 CSC 的分化谱系。我们的结果表明，含有血管内皮的 CSC 的分化后代在调节 CSC 的特性方面发挥着重要作用。因此，miPS-LLCcm 细胞创造了自己的体外生态位，以在分化 CSC 的层次结构中维持自身。
