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.