A biophysical model uncovers the size distribution of migrating cell clusters across cancer types

Migration from the primary tumor is a crucial step in the metastatic cascade. Cells with various degrees of adhesion and motility migrate into the bloodstream as single circulating tumor cells (CTCs) or multi-cellular CTC clusters. The frequency and size distributions of these clusters have been recently measured, but the underlying mechanisms enabling these different modes of migration remain poorly understood. We present a biophysical model that couples intra-tumoral heterogeneity enabled by the epithelial-mesenchymal transition (EMT) with cell migration to explain the modes of individual and collective cancer cell migration. This reduced physical model undergoes a transition from individual migration to collective cell migration and robustly recapitulates CTC cluster fractions and size distributions observed experimentally across several cancer types, thus suggesting the existence of common features in the mechanisms underlying cancer cell migration. Overall, this biophysical model provides a platform to continue to bridge the gap between the molecular and biophysical regulation of cancer cell migration, and highlights that a complete EMT might not be required for metastasis.