Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution
Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution
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DOI：
10.1016/j.celrep.2017.06.010
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发表时间：
2017-07-05
期刊：
影响因子：
8.8
通讯作者：
Ueda, Hiroki R.
中科院分区：
文献类型：
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作者：
Kubota, Shimpei I.;Takahashi, Kei;Ueda, Hiroki R.
从单个细胞开始的随机和增殖事件可以破坏稳态平衡并导致致命的疾病过程，如癌症转移。为了克服转移，有必要在早期阶段检测和量化全身稀疏分布的转移细胞。在这里，我们证明了清晰，通畅的大脑/身体成像鸡尾酒和基于计算分析（CUBIC）的癌症（CUBIC癌症）分析与折射率（RI）=优化的协议，使全面的癌细胞分析的整个身体和器官。我们将CUBIC癌症分析应用于13种小鼠模型，使用9种癌细胞系，并以单细胞分辨率对转移性癌症进展进行时空定量。CUBIC-癌症分析表明，上皮-间充质转化不仅促进外渗，而且促进转移部位的细胞存活。CUBIC-癌症分析也适用于抗肿瘤药物的药效学分析。CUBIC癌症分析与体内生物发光成像和2D组织学兼容。我们认为，这三种模式的可扩展分析管道可能有助于解决目前无法治愈的转移性疾病。
Stochastic and proliferative events initiated from a single cell can disrupt homeostatic balance and lead to fatal disease processes such as cancer metastasis. To overcome metastasis, it is necessary to detect and quantify sparsely distributed metastatic cells throughout the body at early stages. Here, we demonstrate that clear, unobstructed brain/ body imaging cocktails and computational analysis (CUBIC)-based cancer (CUBIC-cancer) analysis with a refractive index (RI)=optimized protocol enables comprehensive cancer cell profiling of the whole body and organs. We applied CUBIC-cancer analysis to 13 mouse models using nine cancer cell lines and spatiotemporal quantification of metastatic cancer progression at single-cell resolution. CUBIC-cancer analysis suggests that the epithelial-mesenchymal transition promotes not only extravasation but also cell survival at metastatic sites. CUBIC-cancer analysis is also applicable to pharmacotherapeutic profiling of anti-tumor drugs. CUBIC-cancer analysis is compatible with in vivo bioluminescence imaging and 2D histology. We suggest that a scalable analytical pipeline with these three modalities may contribute to addressing currently incurable metastatic diseases.