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Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):128-134. doi: 10.1073/pnas.1913511116. Epub 2019 Dec 16.

How tissue fluidity influences brain tumor progression.

Author information

1
Department of Neurology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
2
Department of Radiology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
3
Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
4
Department of Neuroradiology, Universitätsmedizin Leipzig, 04103 Leipzig, Germany.
5
Radiologie Erfurt, 99084 Erfurt, Germany.
6
Division of Soft Matter Physics, Faculty of Physics and Geosciences, 04103 Leipzig, Germany.
7
Department of Radiology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; ingolf.sack@charite.de.

Abstract

Mechanical properties of biological tissues and, above all, their solid or fluid behavior influence the spread of malignant tumors. While it is known that solid tumors tend to have higher mechanical rigidity, allowing them to aggressively invade and spread in solid surrounding healthy tissue, it is unknown how softer tumors can grow within a more rigid environment such as the brain. Here, we use in vivo magnetic resonance elastography (MRE) to elucidate the role of anomalous fluidity for the invasive growth of soft brain tumors, showing that aggressive glioblastomas (GBMs) have higher water content while behaving like solids. Conversely, our data show that benign meningiomas (MENs), which contain less water than brain tissue, are characterized by fluid-like behavior. The fact that the 2 tumor entities do not differ in their soft properties suggests that fluidity plays an important role for a tumor's aggressiveness and infiltrative potential. Using tissue-mimicking phantoms, we show that the anomalous fluidity of neurotumors physically enables GBMs to penetrate surrounding tissue, a phenomenon similar to Saffman-Taylor viscous-fingering instabilities, which occur at moving interfaces between fluids of different viscosity. Thus, targeting tissue fluidity of malignant tumors might open horizons for the diagnosis and treatment of cancer.

KEYWORDS:

glioblastoma; in vivo magnetic resonance elastography; invasive growth; neurotumors; viscous fingering

PMID:
31843897
PMCID:
PMC6955323
[Available on 2020-06-16]
DOI:
10.1073/pnas.1913511116

Conflict of interest statement

The authors declare no competing interest.

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