Multicellular contractility contributes to the emergence of mesothelioma nodules

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.

Malignant pleural mesothelioma nodules remodel their surroundings to vascularize and grow

“…A prominent vasculature in SPC111 tumors develops at a later stage of growth, and the accumulation of a desmoplastic matrix under the tumor nodule plays a key role in the vascularization process. The desmoplastic matrix together with myofibroblasts becomes incorporated into the tumor mass, perhaps by its contractile behavior (44). When the nodule contains enough ECM, it enables ES of the vasculature of the diaphragm.…”