@article{9e50a4ece01d403bbae88db9ac5c5e90,
title = "Rigid tumours contain soft cancer cells",
abstract = "Palpation utilizes the fact that solid breast tumours are stiffer than the surrounding tissue. However, cancer cells tend to soften, which may enhance their ability to squeeze through dense tissue. This apparent paradox proposes two contradicting hypotheses: either softness emerges from adaptation to the tumour{\textquoteright}s microenvironment or soft cancer cells are already present inside a rigid primary tumour mass giving rise to cancer cell motility. We investigate primary tumour explants from patients with breast and cervix carcinomas on multiple length scales. We find that primary tumours are highly heterogeneous in their mechanical properties on all scales from the tissue level down to individual cells. This results in a broad rigidity distribution—from very stiff cells to cells softer than those found in healthy tissue—that is shifted towards a higher fraction of softer cells. Atomic-force-microscopy-based tissue rheology reveals that islands of rigid cells are surrounded by soft cells. The tracking of vital cells confirms the coexistence of jammed and unjammed areas in tumour explants. Despite the absence of a percolated backbone of stiff cells and a large fraction of unjammed, motile cells, cancer cell clusters show a heterogeneous solid behaviour with a finite elastic modulus providing mechanical stability.",
author = "Thomas Fuhs and Franziska Wetzel and Fritsch, {Anatol W.} and Xinzhi Li and Roland Stange and Steve Pawlizak and Kie{\ss}ling, {Tobias R.} and Erik Morawetz and Steffen Grosser and Frank Sauer and J{\"u}rgen Lippoldt and Frederic Renner and Sabrina Friebe and Mareike Zink and Klaus Bendrat and J{\"u}rgen Braun and Oktay, {Maja H.} and John Condeelis and Susanne Briest and Benjamin Wolf and Horn, {Lars Christian} and Michael H{\"o}ckel and Bahriye Aktas and Marchetti, {M Cristina} and Manning, {M. Lisa} and Axel Niendorf and Dapeng Bi and K{\"a}s, {Josef A.}",
note = "Funding Information: We would like to thank A. Bruckert, J. Schnedemann and S. Klingkowski from Pathologie Hamburg-West, as well as F. Juliano from Montefiore Hospital, for the preparation of tissue samples. This work was funded by the German Science Foundation (DFG; KA1116/9-1 and KA1116/17-1), as well as project {\textquoteleft}FORCE{\textquoteright} within the EU{\textquoteright}s Horizon 2020 research and innovation programme. Graduate students A.W.F., T.R.K., S.P. and F.W. were funded by fellowships of the DFG Excellence graduate school BuildMoNa. The research with A.N. was part of the joint project EXPRIMAGE funded by the German Federal Ministry for Education and Research (BMBF 13N9366). T.F. was funded by ERC Advanced Grant {\textquoteleft}HoldCancerBack{\textquoteright} (741350). D.B. and X.L. would like to acknowledge support from the Northeastern University TIER 1 Grant, National Science Foundation DMR-2046683; the Alfred P. Sloan Foundation; MathWorks Microgrants; and the Northeastern University Discovery Cluster. M.H.O. and J.C. were funded by CA255153. We would also like to acknowledge the Syracuse University HTC Campus Grid, NSF award ACI-1341006. Funding Information: We would like to thank A. Bruckert, J. Schnedemann and S. Klingkowski from Pathologie Hamburg-West, as well as F. Juliano from Montefiore Hospital, for the preparation of tissue samples. This work was funded by the German Science Foundation (DFG; KA1116/9-1 and KA1116/17-1), as well as project {\textquoteleft}FORCE{\textquoteright} within the EU{\textquoteright}s Horizon 2020 research and innovation programme. Graduate students A.W.F., T.R.K., S.P. and F.W. were funded by fellowships of the DFG Excellence graduate school BuildMoNa. The research with A.N. was part of the joint project EXPRIMAGE funded by the German Federal Ministry for Education and Research (BMBF 13N9366). T.F. was funded by ERC Advanced Grant {\textquoteleft}HoldCancerBack{\textquoteright} (741350). D.B. and X.L. would like to acknowledge support from the Northeastern University TIER 1 Grant, National Science Foundation DMR-2046683; the Alfred P. Sloan Foundation; MathWorks Microgrants; and the Northeastern University Discovery Cluster. M.H.O. and J.C. were funded by CA255153. We would also like to acknowledge the Syracuse University HTC Campus Grid, NSF award ACI-1341006. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = dec,
doi = "10.1038/s41567-022-01755-0",
language = "English (US)",
volume = "18",
pages = "1510--1519",
journal = "Nature Physics",
issn = "1745-2473",
publisher = "Nature Publishing Group",
number = "12",
}