生物
周细胞
胶质瘤
血脑屏障
癌症研究
干细胞
脑瘤
血管通透性
细胞生物学
病理
内皮干细胞
医学
神经科学
中枢神经系统
体外
内分泌学
生物化学
作者
Wenchao Zhou,Cong Chen,Yu Shi,Qiulian Wu,Ryan C. Gimple,Xiaoguang Fang,Zhi Huang,Kui Zhai,Susan Q. Ke,Yi Ping,Hua Feng,Jeremy Rich,Jennifer Yu,Shideng Bao,Xiu Wu Bian
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2017-11-01
卷期号:21 (5): 591-603.e4
被引量:165
标识
DOI:10.1016/j.stem.2017.10.002
摘要
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy. Eliminating GSC-derived pericytes in xenograft models disrupted BTB tight junctions and increased vascular permeability. We identified BMX as an essential factor for maintaining GSC-derived pericytes. Inhibiting BMX with ibrutinib selectively targeted neoplastic pericytes and disrupted the BTB, but not the BBB, thereby increasing drug effusion into established tumors and enhancing the chemotherapeutic efficacy of drugs with poor BTB penetration. These findings highlight the clinical potential of targeting neoplastic pericytes to significantly improve treatment of brain tumors.
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