Abstract
Metastasizing tumor cells migrate through the surrounding tissue and extracellular matrix toward the blood vessels, in order to colonize distant organs. They typically move in a dense environment, filled with other cells. In this work we study cooperative effects between neighboring cells of different types, migrating in a maze-like environment with directional cue. Using a computerized model, we measure the percentage of cells that arrive to the defined target, for different mesenchymal/amoeboid ratios. Wall degradation of mesenchymal cells, as well as motility of both types of cells, are coupled to metabolic energy-like resource level. We find that indirect cooperation emerges in mid-level energy, as mesenchymal cells create paths that are used by amoeboids. Therefore, we expect to see a small population of mesenchymals kept in a mostly-amoeboid population. We also study different forms of direct interaction between the cells, and show that energy-dependent interaction strength is optimal for the migration of both mesenchymals and amoeboids. The obtained characteristics of cellular cluster size are in agreement with experimental results. We therefore predict that hybrid states, e.g. epithelial-mesenchymal, should be utilized as a stress-response mechanism.
Highlights
Metastasizing tumor cells migrate through the surrounding tissue and extracellular matrix toward the blood vessels, in order to colonize distant organs
In this work we focus on the invasion and migration of cells that have detached from the primary tumor, i.e. have gone through Epithelial-to-Mesenchymal Transition (EMT) or Epithelial-to-Amoeboid Transition (EAT)
Cancer cell migration is a complex process driven by both the cancer cell itself as well as other cells and the surrounding tissue, and involves physical, cellular, and molecular determinants
Summary
When an amoeboid agent encounters a wall, its velocity term that is perpendicular to the wall is zeroed, while the tangent velocity term is unaffected, which results in the agent “sliding” along the wall. When a mesenchymal agent encounters a wall, it may degrade it according to its energetical state (see below)
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