Multicellular contractility contributes to the emergence of mesothelioma nodules

Julia Tarnoki-Zach, Paul Stockhammer, Dona Greta Isai, Elod Mehes, Balint Szeder, Ildiko Kovacs, Edina Bugyik, Sandor Paku, Walter Berger, Sufi Mary Thomas, Zoltan Neufeld, Balazs Dome, Balazs Hegedus, Andras Czirok (Lead / Corresponding author)

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Abstract

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.

Original languageEnglish
Article number20114
Number of pages14
JournalScientific Reports
Volume10
DOIs
Publication statusPublished - 18 Nov 2020

Keywords

  • Biophysics
  • Cancer
  • Cell biology

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