Collective ECM remodeling organizes 3D collective cancer invasion

Tumor metastasis, traditionally considered as random spreading of individual cancer cells, has been shown to also involve coordinated collective invasion in the tissue space. Here we demonstrate experimentally and computationally that physical interactions between cells and extracellular matrix (ECM) support coordinated dissemination of cells from tumor organoids. We find that collective remodeling of the ECM fibrous structure by cell-generated forces produces reciprocal cues to bias cell motility. As a result, dissemination of cells from tumor organoids are controlled by the organoid geometry. Our results indicate that mechanics and geometry are closely coupled in multicellular processes during metastasis and morphogenesis. This study also suggests that migrating cells in 3D ECM represent a distinct class of active particle system where the collective dynamics is governed by the micromechanical remodeling of the environment rather than direct particle-particle interactions.