On-Chip Clonal Analysis of Glioma-Stem-Cell Motility and Therapy Resistance.
On-Chip Clonal Analysis of Glioma-Stem-Cell Motility and Therapy Resistance.
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DOI：
10.1021/acs.nanolett.6b00902
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发表时间：
2016-09-14
期刊：
影响因子：
10.8
通讯作者：
Lee, L. James
中科院分区：
文献类型：
--
作者：
Gallego-Perez, Daniel;Chang, Lingqian;Shi, Junfeng;Ma, Junyu;Kim, Sung-Hak;Zhao, Xi;Malkoc, Veysi;Wang, Xinmei;Minata, Mutsuko;Kwak, Kwang J.;Wu, Yun;Lafyatis, Gregory P.;Lu, Wu;Hansford, Derek J.;Nakano, Ichiro;Lee, L. James
关键词：
胶质瘤干细胞（GSC）运动性增强和治疗抵抗被认为在肿瘤细胞的扩散和复发中起关键作用。因此，更好地了解这些细胞传播和耐受治疗的机制可能会导致更有效的治疗。在这里，我们介绍了一种新的微/纳米技术使能的芯片平台，用于以单克隆分辨率对患者来源的GSC进行活细胞询问。芯片分析显示，两个GSC群体之间的单克隆运动谱存在显著的肿瘤间差异（>10倍），这与肿瘤异种移植实验和基因表达分析的结果密切相关。进一步基于芯片的检查更具侵略性的GSC人口发现显着的克隆间的运动能力的变化（高达104倍），以及在单细胞水平的基因表达谱。使用化疗剂（即，替莫唑胺）和寡RNA（抗miR 363）显示了具有强抗凋亡行为以及增强的运动能力的CD 44-高GSC亚群。本文所述的活细胞询问芯片平台能够以单细胞分辨率对异质癌细胞群体进行彻底和大规模的实时监测，这是任何其他现有技术无法实现的，因此有可能为调节神经胶质瘤干细胞播散和治疗抗性的细胞和分子机制提供新的见解。
Enhanced glioma-stem-cell (GSC) motility and therapy resistance are considered to play key roles in tumor cell dissemination and recurrence. As such, a better understanding of the mechanisms by which these cells disseminate and withstand therapy could lead to more efficacious treatments. Here, we introduce a novel micro-/nanotechnology-enabled chip platform for performing live-cell interrogation of patient-derived GSCs with single-clone resolution. On-chip analysis revealed marked intertumoral differences (>10-fold) in single-clone motility profiles between two populations of GSCs, which correlated well with results from tumor-xenograft experiments and gene-expression analyses. Further chip-based examination of the more-aggressive GSC population revealed pronounced interclonal variations in motility capabilities (up to ∼4-fold) as well as gene-expression profiles at the single-cell level. Chip-supported therapy resistance studies with a chemotherapeutic agent (i.e., temozolomide) and an oligo RNA (anti-miR363) revealed a subpopulation of CD44-high GSCs with strong antiapoptotic behavior as well as enhanced motility capabilities. The living-cell-interrogation chip platform described herein enables thorough and large-scale live monitoring of heterogeneous cancer-cell populations with single-cell resolution, which is not achievable by any other existing technology and thus has the potential to provide new insights into the cellular and molecular mechanisms modulating glioma-stem-cell dissemination and therapy resistance.
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DOI：
10.1158/1078-0432.ccr-11-1795
发表时间：
2012-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Miyazaki T;Pan Y;Joshi K;Purohit D;Hu B;Demir H;Mazumder S;Okabe S;Yamori T;Viapiano M;Shin-ya K;Seimiya H;Nakano I
通讯作者：
Nakano I
影响因子：
6.1
作者：
Gallego-Perez, Daniel;Higuita-Castro, Natalia;Hansford, Derek J.
通讯作者：
Hansford, Derek J.
影响因子：
23.9
作者：
Pietras, Alexander;Katz, Amanda M.;Ekstroem, Elin J.;Wee, Boyoung;Halliday, John J.;Pitter, Kenneth L.;Werbeck, Jillian L.;Amankulor, Nduka M.;Huse, Jason T.;Holland, Eric C.
通讯作者：
Holland, Eric C.
影响因子：
4.1
作者：
Nakano, Ichiro
通讯作者：
Nakano, Ichiro
影响因子：
6.1
作者：
Khine, M;Lau, A;Lee, LP
通讯作者：
Lee, LP