Using cancer cell motility to predict the final morphology of the tumor*

During cancer progression, cancer cells migrate and invade using both individual and collective strategies. While numerous studies have explored how cancer cells form a primary tumor and migrate away to metastasize, less is known about how these migratory strategies contribute to the morphology of the tumor. In this study, we generate three-dimensional engineered spheroids of triple-negative breast cancer cells, comprising two clonal subpopulations with epithelial and mesenchymal characteristics. Epithelial-like spheroids grow and expand, whereas mesenchymal-like spheroids invade and give rise to irregular tumor morphologies. Unexpectedly, experiments monitoring multicellular dynamics, suggest that migratory patterns might be responsible for the different morphologies observed in the tumor spheroids. The mesenchymal subpopulation exhibits directed motility and higher speeds compared to the epithelial subpopulation, consistent with the invasions observed to emanate from the spheroids. Conversely, the epithelial subpopulation maintains consistent interactions with neighboring cells and tends to move in a diffusive manner, in line with the constrained growth of these spheroids. We rationalize these results by developing a minimal 3D agent-based model that quantitatively describes the observed cell motion, and enables us to predict the final tumor morphology. We anticipate that the combination of experiments and computational framework will enable the prediction of cancer progression across a broad range of cancer types and cellular processes.