Geometric dependence of 3D collective cancer invasion

Abstract Metastasis of mesenchymal tumor cells is traditionally considered as a single cell process. Here we report an emergent collective phenomenon where the dissemination rate of mesenchymal breast cancer cells from 3D tumors depends on the tumor geometry. Combining experimental measurements and computational modeling we demonstrate that the collective dynamics is coordinated by the mechanical feedback between individual cells and their surrounding extracellular matrix (ECM). We find the tissue-like fibrous ECM supports long-range physical interactions between cells, which turn geometric cues into regulated cell dissemination dynamics. Our results suggest that migrating cells in 3D ECM represent a distinct class of active particle system where the collective dynamics is governed by remodeling of the environment rather than direct particle-particle interactions.