A Proposed Quantitative Index for Assessing the Potential Contribution of Reprogramming to Cancer Stem Cell Kinetics

[摘要] Enrichment of cancer stem cells (CSCs) is thought to be responsible for glioblastoma multiforme (GBM) recurrence after radiation therapy. Simulation results from our agent-based cellular automata model reveal that the enrichment of CSCs may result either from an increased symmetric self-renewal division rate of CSCs or a reprogramming of non-stem cancer cells (CCs) to a stem cell state.Based onplateau-to-peakratio of the CSC fraction in the tumor following radiation, a downward trend from peak to subsequent plateau (i.e., aplateau-to-peakratio exceeding 1.0) was found to be inconsistent with increased symmetric division alone and favors instead a strong reprogramming component. The two contributions together are seen to be the product of a dynamic equilibrium between CSCs and CCs that is highly regulated by the kinetics of single cells, including the potential for CCs to reacquire a stem cell state and confer phenotypic plasticity to the population as a whole.We conclude that tumor malignancy can be gauged by a degree of cancer cell plasticity.

[学科分类] 生物技术