Tumor spheroids accelerate persistently invading cancer cells.

Glioblastoma brain tumors form in the brain's white matter and remain one of the most lethal cancers despite intensive therapy and surgery. The complex morphology of these tumors includes infiltrative growth and gain of cell motility. Therefore, various brain-mimetic model systems have been developed to investigate invasion dynamics. Despite this, exactly how gradients of cell density, chemical signals and metabolites influence individual cells' migratory behavior remains elusive. Here we show that the gradient field induced by the spheroid-accelerates cells' invasion of the extracellular matrix. We show that cells are pushed away from the spheroid along a radial gradient, as predicted by a biased persistent random walk. Thus, our results grasp in a simple model the complex behavior of metastasizing cells. We anticipate that this well-defined and quantitative assay could be instrumental in the development of new anti-cancer strategies.

Single-cell tracking reveals super-spreading brain cancer cells with high persistence.

Cell migration is a fundamental characteristic of vital processes such as tissue morphogenesis, wound healing and immune cell homing to lymph nodes and inflamed or infected sites. Therefore, various brain defect diseases, chronic inflammatory diseases as well as tumor formation and metastasis are associated with aberrant or absent cell migration. We embedded multicellular brain cancer spheroids in Matrigel™ and utilized single-particle tracking to extract the paths of cells migrating away from the spheroids. We found that - in contrast to local invasion - single cell migration is independent of Matrigel™ concentration and is characterized by high directionality and persistence. Furthermore, we identified a subpopulation of super-spreading cells with >200-fold longer persistence times than the majority of cells. These results highlight yet another aspect of cell heterogeneity in tumors.