title: Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts.
abstract: Tumors are often heterogeneous in which tumor cells of different phenotypes have distinct properties. For scientific and clinical interests, it is of fundamental importance to understand their properties and the dynamic variations among different phenotypes, specifically under radio- and/or chemo-therapy. Currently there are two controversial models describing tumor heterogeneity, the cancer stem cell (CSC) model and the stochastic model. To clarify the controversy, we measured probabilities of different division types and transitions of cells via in situ immunofluorescence. Based on the experiment data, we constructed a model that combines the CSC with the stochastic concepts, showing the existence of both distinctive CSC subpopulations and the stochastic transitions from NSCCs to CSCs. The results showed that the dynamic variations between CSCs and non-stem cancer cells (NSCCs) can be simulated with the model. Further studies also showed that the model can be used to describe the dynamics of the two subpopulations after radiation treatment. More importantly, analysis demonstrated that the experimental detectable equilibrium CSC proportion can be achieved only when the stochastic transitions from NSCCs to CSCs occur, indicating that tumor heterogeneity may exist in a model coordinating with both the CSC and the stochastic concepts. The mathematic model based on experimental parameters may contribute to a better understanding of the tumor heterogeneity, and provide references on the dynamics of CSC subpopulation during radiotherapy.
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Weikang
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Quan
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Gen
authors.initials: G
authors.lastname: Yang
authors.affiliation: Center for Microfluidic and Nanotechnology, The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Chunxiong
authors.initials: C
authors.lastname: Luo
authors.affiliation: Center for Microfluidic and Nanotechnology, The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, P. R. China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D007700:Kinetics; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000528:radiation effects; D013269:Stochastic Processes