TY - JOUR
T1 - Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity
AU - Tanaka, Nobuyuki
AU - Kanatani, Shigeaki
AU - Tomer, Raju
AU - Sahlgren, Cecilia
AU - Kronqvist, Pauliina
AU - Kaczynska, Dagmara
AU - Louhivuori, Lauri
AU - Kis, Lorand
AU - Lindh, Claes
AU - Mitura, Przemysław
AU - Stepulak, Andrzej
AU - Corvigno, Sara
AU - Hartman, Johan
AU - Micke, Patrick
AU - Mezheyeuski, Artur
AU - Strell, Carina
AU - Carlson, Joseph W.
AU - Fernández Moro, Carlos
AU - Dahlstrand, Hanna
AU - Östman, Arne
AU - Matsumoto, Kazuhiro
AU - Wiklund, Peter
AU - Oya, Mototsugu
AU - Miyakawa, Ayako
AU - Deisseroth, Karl
AU - Uhlén, Per
N1 - Funding Information:
The authors would like to thank J. Szumiło, Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland for kindly providing human tissue samples. This study was supported by the Swedish Research Council (grants 2009-3364, 2010-4392 and 2013-3189 to P.U.), the Swedish Cancer Society (grant CAN2013/802 and CAN2016/801 to P.U.), the Swedish Brain Foundation (grant FO2017/0107 to P.U.), the Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM) (P.U.), a Knut and Alice Wallenberg Foundation Grant to the Center for Live Imaging of Cells at the Karolinska (CLICK) Institutet (P.U.), the Royal Swedish Academy of Sciences (P.U.), the David and Astrid Hagelén Foundation (N.T.), the Takeda Science Foundation (N.T.), the Scandinavia-Japan Sasakawa Foundation (N.T. and S.K.), and the Wenner-Gren Foundation (S.K.). The light-sheet microscopy infrastructure used in this work received grants from the Strategic Research Area in Neuroscience – StratNeuro and the Strategic Research Area in Stem Cells and Regenerative Medicine – StratRegen supported by the Swedish government.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogeneity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin-embedded (FFPE) biopsy samples. We also show that cleared FFPE samples can be re-embedded in paraffin after examination for future use, and that our tumour-phenotyping pipeline can determine tumour stage and stratify patient prognosis from clinical samples with higher accuracy than current diagnostic methods, thus facilitating the design of more efficient cancer therapies.
AB - Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogeneity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin-embedded (FFPE) biopsy samples. We also show that cleared FFPE samples can be re-embedded in paraffin after examination for future use, and that our tumour-phenotyping pipeline can determine tumour stage and stratify patient prognosis from clinical samples with higher accuracy than current diagnostic methods, thus facilitating the design of more efficient cancer therapies.
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U2 - 10.1038/s41551-017-0139-0
DO - 10.1038/s41551-017-0139-0
M3 - Article
C2 - 31015588
AN - SCOPUS:85034610370
SN - 2157-846X
VL - 1
SP - 796
EP - 806
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 10
ER -
