Tumour-stromal interactions generate emergent persistence in collective cancer cell migration

Cancer cell collective migration is a complex behaviour leading to the invasion of cancer cells into surrounding tissue, often with the aid of stromal cells in the microenvironment, such as macrophages or fibroblasts. Although tumour-tumour and tumour-stromal intercellular signalling have been shown to contribute to cancer cell migration,we lack a fundamental theoretical understanding of howaggressive invasion emerges fromthe synergy between these mechanisms. We use a computational self-propelled particle model to simulate intercellular interactions between co-migrating tumour and stromal cells and study the emergence of collective movement. We find that tumour-stromal interaction increases the cohesion and persistence of migrating mixed tumour-stromal cell clusters in a noisy and unbounded environment, leading to increased cell cluster size and distance migrated by cancer cells. Although environmental constraints, such as vasculature or extracellular matrix, influence cancer migration in vivo, our model shows that cell-cell interactions are sufficient to generate cohesive and persistent movement. From our results, we conclude that inhibition of tumour-stromal intercellular signalling may present a viable therapeutic target for disrupting collective cancer cell migration.