Targeting JNK for therapeutic depletion of stem-like glioblastoma cells

被引:78
作者
Matsuda, Ken-ichiro [1 ,2 ]
Sato, Atsushi [1 ,2 ]
Okada, Masashi [1 ]
Shibuya, Keita [1 ]
Seino, Shizuka [1 ]
Suzuki, Kaori [1 ,3 ]
Watanabe, Eriko [1 ]
Narita, Yoshitaka [3 ]
Shibui, Soichiro [3 ]
Kayama, Takamasa [2 ]
Kitanaka, Chifumi [1 ,4 ,5 ]
机构
[1] Yamagata Univ, Sch Med, Dept Mol Canc Sci, Yamagata 9909585, Japan
[2] Yamagata Univ, Sch Med, Dept Neurosurg, Yamagata 9909585, Japan
[3] Natl Canc Ctr, Div Neurosurg, Tokyo 1040045, Japan
[4] Yamagata Univ, Res Inst Adv Mol Epidemiol, Oncol Res Ctr, Yamagata 9909585, Japan
[5] Japan Soc Promot Sci, Global COE Program Med Sci, Tokyo 1028472, Japan
来源
SCIENTIFIC REPORTS | 2012年 / 2卷
基金
日本学术振兴会;
关键词
PROTECTS DOPAMINERGIC-NEURONS; EXPRESSION; INHIBITOR; GLIOMA; ACTIVATION; TEMOZOLOMIDE; SP600125; MODEL; TUMORIGENICITY; MECHANISMS;
D O I
10.1038/srep00516
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Control of the stem-like tumour cell population is considered key to realizing the long-term survival of patients with glioblastoma, one of the most devastating human malignancies. To date, possible therapeutic targets and targeting methods have been described, but none has yet proven to target stem-like glioblastoma cells in the brain to the extent necessary to provide a survival benefit. Here we show that targeting JNK in vivo, the activity of which is required for the maintenance of stem-like glioblastoma cells, via transient, systemic administration of a small-molecule JNK inhibitor depletes the self-renewing and tumour-initiating populations within established tumours, inhibits tumour formation by stem-like glioblastoma cells in the brain, and provide substantial survival benefit without evidence of adverse events. Our findings not only implicate JNK in the maintenance of stem-like glioblastoma cells but also demonstrate that JNK is a viable, clinically relevant therapeutic target in the control of stem-like glioblastoma cells.
引用
收藏
页数:11
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