Multicellular contractility contributes to the emergence of mesothelioma nodules

Malignant pleural mesothelioma (MPM) has an overall poor prognosis and unsatisfactory treatment options. MPM nodules, protruding into the pleural cavity may have growth and spreading dynamics distinct that of other solid tumors. We demonstrate that multicellular aggregates can develop spontaneously in the majority of tested MPM cell lines when cultured at high cell density. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Prominent actin cables, spanning several cells, are abundant both in cultured aggregates and in MPM surgical specimens. We propose a computational model for in vitro MPM nodule development. Such a self-tensioned Maxwell fluid exhibits a pattern-forming instability that was studied by analytical tools and computer simulations. Altogether, our findings may underline a rational for targeting the actomyosin system in MPM.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Scientific reports - 10(2020), 1 vom: 18. Nov., Seite 20114

Sprache:

Englisch

Beteiligte Personen:

Tarnoki-Zach, Julia [VerfasserIn]
Stockhammer, Paul [VerfasserIn]
Isai, Dona Greta [VerfasserIn]
Mehes, Elod [VerfasserIn]
Szeder, Balint [VerfasserIn]
Kovacs, Ildiko [VerfasserIn]
Bugyik, Edina [VerfasserIn]
Paku, Sandor [VerfasserIn]
Berger, Walter [VerfasserIn]
Thomas, Sufi Mary [VerfasserIn]
Neufeld, Zoltan [VerfasserIn]
Dome, Balazs [VerfasserIn]
Hegedus, Balazs [VerfasserIn]
Czirok, Andras [VerfasserIn]

Links:

Volltext

Themen:

138381-45-0
20WC4J7CQ6
Actins
Amides
Blebbistatin
EC 3.6.4.1
Heterocyclic Compounds, 4 or More Rings
Journal Article
Myosins
Pyridines
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media
Y 27632

Anmerkungen:

Date Completed 22.04.2021

Date Revised 22.04.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-020-76641-x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317760335