Abnormal Aggregation of Invasive Cancer Cells Induced by Collective Polarization and ECM-Mediated Mechanical Coupling in Coculture Systems

Abstract

Studies on pattern formation in coculture cell systems can provide insights into many physiological and pathological processes. Here, we investigate how the extracellular matrix (ECM) may influence the patterning in coculture systems. The model coculture system we use is composed of highly motile invasive breast cancer cells, initially mixed with inert nonmetastatic cells on a 2D substrate and covered with a Matrigel layer introduced to mimic ECM. We observe that the invasive cells exhibit persistent centripetal motion and yield abnormal aggregation, rather than random spreading, due to a “collective pulling” effect resulting from ECM-mediated transmission of active contractile forces generated by the polarized migration of the invasive cells along the vertical direction. The mechanism we report may open a new window for the understanding of biological processes that involve multiple types of cells.