Enrichment of cancer stem cells (CSCs) is thought to be responsible for glioblastomamultiforme (GBM) recurrence after radiation\ntherapy. Simulation results fromour agent-based cellular automatamodel reveal that the enrichment of CSCs may result either from\nan increased symmetric self-renewal division rate of CSCs or a reprogramming of non-stem cancer cells (CCs) to a stem cell state.\nBased on plateau-to-peak ratio of the CSC fraction in the tumor following radiation, a downward trend from peak to subsequent\nplateau (i.e., a plateau-to-peak ratio exceeding 1.0) was found to be inconsistent with increased symmetric division alone and favors\ninstead a strong reprogramming component. The two contributions together are seen to be the product of a dynamic equilibrium\nbetween CSCs and CCs that is highly regulated by the kinetics of single cells, including the potential for CCs to reacquire a stem\ncell state and confer phenotypic plasticity to the population as a whole. We conclude that tumor malignancy can be gauged by a\ndegree of cancer cell plasticity.
Loading....