title: A proposed quantitative index for assessing the potential contribution of reprogramming to cancer stem cell kinetics.
abstract: 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.
authors: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, 736 Cambridge Street, SEMC-CBR1, Boston, MA 02135, USA.
authors: Xuefeng
authors: 0000-0002-1904-392X
authors: X
authors: Gao
authors: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, 736 Cambridge Street, SEMC-CBR1, Boston, MA 02135, USA.
authors: J Tyson
authors: 0000-0003-1955-6052
authors: JT
authors: McDonald
authors: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, 736 Cambridge Street, SEMC-CBR1, Boston, MA 02135, USA.
authors: Mamta
authors: M
authors: Naidu
authors: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, 736 Cambridge Street, SEMC-CBR1, Boston, MA 02135, USA.
authors: Philip
authors: P
authors: Hahnfeldt
authors: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, 736 Cambridge Street, SEMC-CBR1, Boston, MA 02135, USA.
authors: Lynn
authors: L
authors: Hlatky