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Stem Cells International
Volume 2014, Article ID 249309, 8 pages
http://dx.doi.org/10.1155/2014/249309
Research Article

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

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

Received 22 January 2014; Revised 17 April 2014; Accepted 17 April 2014; Published 12 May 2014

Academic Editor: Gary E. Lyons

Copyright © 2014 Xuefeng Gao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.