Cancer cells in the tumor core exhibit spatially coordinated migration patterns

Abstract

In the early stages ofmetastasis, cancercells exit the primary tumorand enter the vasculature. Althoughmost studieshave focused onthe tumor invasive front, cancer cells from the tumor core can also potentially metastasize.To address cellmotility inthe tumorcore,we imagedtumor explants from spontaneously forming tumors in mice in real time using long-term two-photon microscopy. Cancer cells in the tumor core are remarkably dynamic and exhibit correlated migration patterns, giving rise to local 'currents' and large-scale tissue dynamics. Although cells exhibit stop-and-start migration with intermittent pauses, pausing does not appear to be required during division. Use of pharmacological inhibitors indicates that migration patterns in tumors are actively driven by the actin cytoskeleton. Under these conditions, we also observed a relationship between migration speed and correlation length, suggesting that cells in tumors are near a jamming transition. Our study provides newinsight into the dynamics of cancercells inthe tumor core, opening new avenues of research in understanding the migratory properties of cancer cells and later metastasis.