Journal
CELL REPORTS
Volume 20, Issue 1, Pages 236-250Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.06.010
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Funding
- AMED-CREST (Japan Agency for Medical Research and Development [AMED]/Ministry of Education, Culture, Sports, Science and Technology, Japan [MEXT])
- CREST (JST/MEXT)
- Brain/MINDS (AMED/MEXT)
- Basic Science and Platform Technology Program for Innovative Biological Medicine (AMED/MEXT)
- Japan Society for the Promotion of Science (JSPS) (KAKENHI) [14J01180, 17J30007, 13J10991, 16J05993]
- JSPS KAKENHI [16K15124, 25221004, 15H05774, 23115006]
- Brain Protein Aging and Dementia Control from MEXT [17H05688]
- grant for Practical Research for Innovative Cancer Control, AMED [16ck0106193h0001]
- Tokyo Society of Medical Sciences
- Grants-in-Aid for Scientific Research [15H05774, 17H05688, 13J10991, 17J30007, 14J01180, 16J05993, 16K15124] Funding Source: KAKEN
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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.
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