Cancer stem cells maintain a hierarchy of differentiation by creating their niche.
Cancer stem cells maintain a hierarchy of differentiation by creating their niche.
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DOI：
10.1002/ijc.28648
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发表时间：
2014-07-01
影响因子：
6.4
通讯作者：
Seno, Masaharu
中科院分区：
文献类型：
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作者：
Matsuda, Shuichi;Yan, Ting;Mizutani, Akifumi;Sota, Tatsuyuki;Hiramoto, Yuki;Prieto-Vila, Marta;Chen, Ling;Satoh, Ayano;Kudoh, Takayuki;Kasai, Tomonari;Murakami, Hiroshi;Fu, Li;Salomon, David S.;Seno, Masaharu
癌症干细胞（CSC）的自我更新和分化特性由CSC生态位调节和维持。然而，这种维持的机制，特别是分化的癌细胞所贡献的维持，仍有待充分阐明。最近，我们建立了来自小鼠诱导多能干细胞（miPSC）的CSCs模型，miPS-LLCcm。体外培养的 miPS-LLCcm 细胞与干细胞样细胞和包括血管内皮细胞在内的分化细胞自主平衡。在这些条件下，在存在分化细胞分泌的因子的情况下，CSC 特性似乎是稳定的。该因子激活 Notch 信号传导并促进 CSC 的自我更新。此外，分泌因子似乎调节 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 细胞在体外创建自己的生态位，以将自己维持在分化的 CSC 层次结构中。癌症干细胞通过在支持性微环境中扎根而造成破坏，该微环境为自我更新和分化提供所需的因子。但微环境或生态位如何维持干细胞呢？为了进行研究，这些作者在体外建立了 CSC 系统，并评估 CSC 的后代细胞是否需要留在附近以创建干细胞生态位。他们发现，分化的子代细胞确实释放出维持干细胞自我更新和分化之间平衡的因子，部分是通过Notch信号通路实现的。了解这种动态将有助于研究人员制定阻碍癌症干细胞扎根的能力的策略。
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. Cancer stem cells wreak their devastation by taking root in a supportive microenvironment that provides needed factors for both self-renewal and differentiation. But how does the microenvironment, or niche, sustain the stem cells? To investigate, these authors established a CSC system in vitro and assessed whether the progeny cells of CSCs need to stay nearby to create the stem cell niche. They found that the differentiated progeny cells do release factors that maintain the balance between self-renewal and differentiation in the stem cells, in part through the Notch signaling pathway. Understanding this dynamic will help researchers develop strategies to hinder cancer stem cells' ability to take hold.
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影响因子：
7.5
作者：
Holland, Jane D.;Klaus, Alexandra;Birchmeier, Walter
通讯作者：
Birchmeier, Walter
影响因子：
64.8
作者：
Ricci-Vitiani, Lucia;Pallini, Roberto;De Maria, Ruggero
通讯作者：
De Maria, Ruggero
影响因子：
11.2
作者：
Zhu TS;Costello MA;Talsma CE;Flack CG;Crowley JG;Hamm LL;He X;Hervey-Jumper SL;Heth JA;Muraszko KM;DiMeco F;Vescovi AL;Fan X
通讯作者：
Fan X
Sonic Hedgehog 通路对于维持人类胃癌中的癌症干细胞样细胞至关重要。
影响因子：
3.7
作者：
Song Z;Yue W;Wei B;Wang N;Li T;Guan L;Shi S;Zeng Q;Pei X;Chen L
通讯作者：
Chen L
DOI：
10.1158/1078-0432.ccr-09-2846
发表时间：
2010-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Merchant AA;Matsui W
通讯作者：
Matsui W