| Abstract: |
| Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. We present a multi-cell, virtual-tissue model of tumor somatic evolution, which includes essential cell behaviors, microenvironmental components and their interactions. The self organized gradients created by the growing tumor lead to regions with different cell survival rates, driving the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors. |
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