A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages.
A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages.
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DOI：
10.1038/ncb3041
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发表时间：
2014-11
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞生物学程序被称为上皮-间充质转化（EMT），赋予癌细胞间充质特性和进入癌症干细胞（CSC）状态的能力。然而，csc与其周围微环境之间的相互作用尚不清楚。本研究表明，肿瘤相关的单核细胞和巨噬细胞（tam）通过与csc的近分泌信号产生csc生态位。我们进行了定量的蛋白质组学分析，发现EMT程序上调CD90/Thy1和EphA4的表达，这两种基因通过直接与细胞上各自的对抗受体结合来介导CSCs与tam的物理相互作用。作为回应，癌细胞上的EphA4受体激活Src和NF-κB，后者导致csc分泌多种细胞因子；这些细胞因子用于维持干细胞状态。事实上，混合巨噬细胞增强了癌细胞的CSC活性。这些发现强调了tam作为CSC生态位重要组成部分的重要性。
The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. However, the interactions between CSCs and their surrounding microenvironment are poorly understood. Here we show that tumor-associated monocytes and macrophages (TAMs) create a CSC-niche via juxtacrine signaling with CSCs. We performed quantitative proteomic profiling and found that the EMT program upregulates the expression of CD90/Thy1 and EphA4, which mediate the physical interactions of CSCs with TAMs by directly binding with their respective counter-receptors on these cells. In response, the EphA4 receptor on the carcinoma cells activates Src and NF-κB, the latter results in the secretion of a variety of cytokines by the CSCs; these cytokines serve to sustain the stem-cell state. Indeed, admixed macrophages enhance the CSC activities of carcinoma cells. These findings underscore the significance of TAMs as important components of the CSC niche.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
DOI：
10.1016/j.bbamcr.2008.10.004
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Barker TH;Hagood JS
通讯作者：
Hagood JS
影响因子：
50.3
作者：
Binda E;Visioli A;Giani F;Lamorte G;Copetti M;Pitter KL;Huse JT;Cajola L;Zanetti N;DiMeco F;De Filippis L;Mangiola A;Maira G;Anile C;De Bonis P;Reynolds BA;Pasquale EB;Vescovi AL
通讯作者：
Vescovi AL
影响因子：
7
作者：
He, Jintang;Liu, Yashu;Lubman, David M.
通讯作者：
Lubman, David M.
影响因子：
64.5
作者：
Gupta PB;Onder TT;Jiang G;Tao K;Kuperwasser C;Weinberg RA;Lander ES
通讯作者：
Lander ES