Cell and Nucleus Shape as an Indicator of Tissue Fluidity in Carcinoma

Tissue, cell, and nucleus morphology change during tumor progression. In 2D confluent cell cultures, different tissue states, such as fluid (unjammed) and solid (jammed), are correlated with cell shapes. These results do not have to apply a priori to three dimensions. Cancer cell motility requires a...

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Published inPhysical review. X Vol. 11; no. 1; p. 011033
Main Authors Grosser, Steffen, Lippoldt, Jürgen, Oswald, Linda, Merkel, Matthias, Sussman, Daniel M., Renner, Frédéric, Gottheil, Pablo, Morawetz, Erik W., Fuhs, Thomas, Xie, Xiaofan, Pawlizak, Steve, Fritsch, Anatol W., Wolf, Benjamin, Horn, Lars-Christian, Briest, Susanne, Aktas, Bahriye, Manning, M. Lisa, Käs, Josef A.
Format Journal Article
LanguageEnglish
Published College Park American Physical Society 01.02.2021
Subjects
Biological Physics
Cancer
Condensed Matter
Correlation
Diagnosis
Disordered Systems and Neural Networks
Elongation
Fluidizing
Jamming
Mechanical properties
Morphology
Motility
Nuclei (cytology)
Physics
Soft Condensed Matter
Spheroids
Statistical Mechanics
Tracking
Tumors
Viscosity
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Summary:Tissue, cell, and nucleus morphology change during tumor progression. In 2D confluent cell cultures, different tissue states, such as fluid (unjammed) and solid (jammed), are correlated with cell shapes. These results do not have to apply a priori to three dimensions. Cancer cell motility requires and corresponds to a fluidization of the tumor tissue on the bulk level. Here, we investigate bulk tissue fluidity in 3D and determine how it correlates with cell and nucleus shape. In patient samples of mamma and cervix carcinoma, we find areas where cells can move or are immobile. We compare 3D cell spheroids composed of cells from a cancerous and a noncancerous cell line. Through bulk mechanical spheroid-fusion experiments and single live-cell tracking, we show that the cancerous sample is fluidized by active cells moving through the tissue. The healthy, epithelial sample with immobile cells behaves more solidlike. 3D segmentations of the samples show that the degree of tissue fluidity correlates with elongated cell and nucleus shapes. This correlation links cell shapes to cell motility and bulk mechanical behavior. We find two active states of matter in solid tumors: an amorphous glasslike state with characteristics of 3D cell jamming and a disordered fluid state. Individual cell and nucleus shape may serve as a marker for metastatic potential to foster personalized cancer treatment.
ISSN:2160-3308
2160-3308
DOI:10.1103/PhysRevX.11.011033