生物
癌变
巨噬细胞
免疫系统
效应器
抽搐
细胞生物学
癌症研究
免疫学
体内
体外
癌症
神经科学
遗传学
作者
Xiaohong Guo,Yang Zhao,Huan Yan,Yuting Yang,Shuying Shen,Xiaoming Dai,Xinyan Ji,Feiyang Ji,Xingguo Gong,Li Li,Xueli Bai,Xin‐Hua Feng,Tingbo Liang,Junfang Ji,Lei Chen,Hongyang Wang,Bin Zhao
出处
期刊:Genes & Development
[Cold Spring Harbor Laboratory]
日期:2017-02-01
卷期号:31 (3): 247-259
被引量:206
标识
DOI:10.1101/gad.294348.116
摘要
Tumor infiltrated type II (M2) macrophages promote tumorigenesis by suppressing immune clearance, promoting proliferation, and stimulating angiogenesis. Interestingly, macrophages were also found to enrich in small foci of altered hepatocytes containing liver tumor-initiating cells (TICs). However, whether and how TICs specifically recruit macrophages and the function of these macrophages in tumor initiation remain unknown due to technical difficulties. In this study, by generating genetically defined liver TICs, we demonstrate that TICs actively recruit M2 macrophages from as early as the single-cell stage. Elimination of TIC-associated macrophages (TICAMs) abolishes tumorigenesis in a manner dependent on the immune system. Mechanistically, activation of the Hippo pathway effector Yes-associated protein (YAP) underlies macrophage recruitment by TICs. These results demonstrate for the first time that macrophages play a decisive role in the survival of single TICs in vivo and provide a proof of principle for TIC elimination by targeting YAP or M2 macrophages.
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