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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Main Authors: Shimpei I. Kubota, Kei Takahashi, Jun Nishida, Yasuyuki Morishita, Shogo Ehata, Kazuki Tainaka, Kohei Miyazono, Hiroki R. Ueda
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717308069
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spelling 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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