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Stem Cells Int. 2014;2014:249309. doi: 10.1155/2014/249309. Epub 2014 May 12.

A proposed quantitative index for assessing the potential contribution of reprogramming to cancer stem cell kinetics.

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Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, 736 Cambridge Street, SEMC-CBR1, Boston, MA 02135, USA.


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 on plateau-to-peak ratio of the CSC fraction in the tumor following radiation, a downward trend from peak to subsequent plateau (i.e., a plateau-to-peak ratio 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.

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