Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts

PLoS One. 2014 Jan 9;9(1):e84654. doi: 10.1371/journal.pone.0084654. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Kinetics
  • Models, Biological*
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / radiation effects
  • Stochastic Processes

Grants and funding

This work was supported by grants from the Key Project of National Natural Science Foundation of China (10935009), the National Science Foundation for Young Scholars of China (31000383) and the National Grand Instrument Program (2012YQ030142). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.