Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution
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. He...
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doaj-274b934335aa4e7ab758797f0734ba2a2020-11-25T00:19:05ZengElsevierCell Reports2211-12472017-07-0120123625010.1016/j.celrep.2017.06.010Whole-Body Profiling of Cancer Metastasis with Single-Cell ResolutionShimpei I. Kubota0Kei Takahashi1Jun Nishida2Yasuyuki Morishita3Shogo Ehata4Kazuki Tainaka5Kohei Miyazono6Hiroki R. Ueda7Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanStochastic 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.http://www.sciencedirect.com/science/article/pii/S2211124717308069tissue clearingwhole-body profilingcancer metastasisCUBIC-cancer analysis3D cancer atlastumor microenvironmentepithelial-mesenchymal transitionpharmacotherapeutic profiling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shimpei I. Kubota Kei Takahashi Jun Nishida Yasuyuki Morishita Shogo Ehata Kazuki Tainaka Kohei Miyazono Hiroki R. Ueda |
spellingShingle |
Shimpei I. Kubota Kei Takahashi Jun Nishida Yasuyuki Morishita Shogo Ehata Kazuki Tainaka Kohei Miyazono Hiroki R. Ueda Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution Cell Reports tissue clearing whole-body profiling cancer metastasis CUBIC-cancer analysis 3D cancer atlas tumor microenvironment epithelial-mesenchymal transition pharmacotherapeutic profiling |
author_facet |
Shimpei I. Kubota Kei Takahashi Jun Nishida Yasuyuki Morishita Shogo Ehata Kazuki Tainaka Kohei Miyazono Hiroki R. Ueda |
author_sort |
Shimpei I. Kubota |
title |
Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution |
title_short |
Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution |
title_full |
Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution |
title_fullStr |
Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution |
title_full_unstemmed |
Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution |
title_sort |
whole-body profiling of cancer metastasis with single-cell resolution |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-07-01 |
description |
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. |
topic |
tissue clearing whole-body profiling cancer metastasis CUBIC-cancer analysis 3D cancer atlas tumor microenvironment epithelial-mesenchymal transition pharmacotherapeutic profiling |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717308069 |
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