Multicellular contractility contributes to the emergence of mesothelioma nodules

Sci Rep. 2020 Nov 18;10(1):20114. doi: 10.1038/s41598-020-76641-x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Actins / metabolism
  • Amides / pharmacology
  • Animals
  • Cell Count
  • Cell Line, Tumor
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Male
  • Mesothelioma, Malignant / metabolism
  • Mesothelioma, Malignant / pathology*
  • Mice, SCID
  • Myosins / metabolism
  • Pyridines / pharmacology
  • Stochastic Processes
  • Time-Lapse Imaging
  • Xenograft Model Antitumor Assays

Substances

  • Actins
  • Amides
  • Heterocyclic Compounds, 4 or More Rings
  • Pyridines
  • Y 27632
  • blebbistatin
  • Myosins