Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution

doi:10.1016/j.celrep.2017.06.010

. 2017 Jul 5;20(1):236-250.

doi: 10.1016/j.celrep.2017.06.010.

Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution

Shimpei I Kubota¹, Kei Takahashi², Jun Nishida², Yasuyuki Morishita², Shogo Ehata², Kazuki Tainaka³, Kohei Miyazono⁴, Hiroki R Ueda⁵

Affiliations

¹ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan.
⁴ Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: miyazono@m.u-tokyo.ac.jp.
⁵ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, 1-3 Yamadaoka, Suita, Osaka 565-5241, Japan. Electronic address: uedah-tky@umin.ac.jp.

PMID: 28683317
DOI: 10.1016/j.celrep.2017.06.010

Free article

Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution

Shimpei I Kubota et al. Cell Rep. 2017.

Free article

. 2017 Jul 5;20(1):236-250.

doi: 10.1016/j.celrep.2017.06.010.

Authors

Shimpei I Kubota¹, Kei Takahashi², Jun Nishida², Yasuyuki Morishita², Shogo Ehata², Kazuki Tainaka³, Kohei Miyazono⁴, Hiroki R Ueda⁵

Affiliations

¹ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan.
⁴ Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: miyazono@m.u-tokyo.ac.jp.
⁵ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, 1-3 Yamadaoka, Suita, Osaka 565-5241, Japan. Electronic address: uedah-tky@umin.ac.jp.

PMID: 28683317
DOI: 10.1016/j.celrep.2017.06.010

Abstract

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.

Keywords: 3D cancer atlas; CUBIC-cancer analysis; cancer metastasis; epithelial-mesenchymal transition; pharmacotherapeutic profiling; tissue clearing; tumor microenvironment; whole-body profiling.

PubMed Disclaimer

Cited by

Detection and Morphological Analysis of Micro-Ruptured Cortical Arteries in Subdural Hematoma: Three-Dimensional Visualization Using the Tissue-Clearing Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational Analysis Method.
Funayama K, Tainaka K, Koyama A, Katsuragi-Go R, Nishikawa-Harada N, Higuchi R, Aoyama T, Watanabe H, Takahashi N, Takatsuka H. Funayama K, et al. Diagnostics (Basel). 2022 Nov 20;12(11):2875. doi: 10.3390/diagnostics12112875. Diagnostics (Basel). 2022. PMID: 36428935 Free PMC article.
Optical Tissue Clearing to Study the Intra-Pulmonary Biodistribution of Intravenously Delivered Mesenchymal Stromal Cells and Their Interactions with Host Lung Cells.
Pichardo AH, Amadeo F, Wilm B, Lévy R, Ressel L, Murray P, Sée V. Pichardo AH, et al. Int J Mol Sci. 2022 Nov 16;23(22):14171. doi: 10.3390/ijms232214171. Int J Mol Sci. 2022. PMID: 36430651 Free PMC article.
Intracardiac Injection Mouse Model to Study Cancer Cell Dormancy in Brain Metastasis.
Mizutani R, Hirata E. Mizutani R, et al. Methods Mol Biol. 2024;2811:113-122. doi: 10.1007/978-1-0716-3882-8_8. Methods Mol Biol. 2024. PMID: 39037653
Three-dimensional mapping in multi-samples with large-scale imaging and multiplexed post staining.
Chen S, Liu G, Li A, Liu Z, Long B, Yang X, Gong H, Li X. Chen S, et al. Commun Biol. 2023 Feb 3;6(1):148. doi: 10.1038/s42003-023-04456-3. Commun Biol. 2023. PMID: 36737476 Free PMC article.
Intravenous Administration of Human Umbilical Cord Mesenchymal Stromal Cells Leads to an Inflammatory Response in the Lung.
Hernandez Pichardo A, Wilm B, Liptrott NJ, Murray P. Hernandez Pichardo A, et al. Stem Cells Int. 2023 Sep 5;2023:7397819. doi: 10.1155/2023/7397819. eCollection 2023. Stem Cells Int. 2023. PMID: 37705699 Free PMC article.

See all "Cited by" articles

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Other Literature Sources
Research Materials
- National BioResource Project

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution

Affiliations

Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution

Authors

Affiliations

Abstract

Similar articles

Cited by

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials