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Tumor metastasis, traditionally considered as random spreading of individualcancer cells, has been shown to also involve coordinated collective invasion inthe tissue space. Here we demonstrate experimentally and computationally thatphysical interactions between cells and extracellular matrix (ECM) supportcoordinated dissemination of cells from tumor organoids. We find thatcollective remodeling of the ECM fibrous structure by cell-generated forcesproduces reciprocal cues to bias cell motility. As a result, dissemination ofcells from tumor organoids are controlled by the organoid geometry. Our resultsindicate that mechanics and geometry are closely coupled in multicellularprocesses during metastasis and morphogenesis. This study also suggests thatmigrating cells in 3D ECM represent a distinct class of active particle systemwhere the collective dynamics is governed by the micromechanical remodeling ofthe environment rather than direct particle-particle interactions.

Collective ECM remodeling organizes 3D collective cancer invasion