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

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2014 Jun 24

PMID 24955094

Citations 11

Authors

Xuefeng Gao

J Tyson McDonald

Mamta Naidu

Philip Hahnfeldt

Lynn Hlatky

Affiliations

Soon will be listed here.

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.

Citing Articles

Identification of the Gene Expression Rules That Define the Subtypes in Glioma.

Cai Y, Zhang S, Zhang Y, Pan X, Feng K, Chen L J Clin Med. 2018; 7(10).

PMID: 30322114 PMC: 6210469. DOI: 10.3390/jcm7100350.

Contribution of the Wnt Pathway to Defining Biology of Glioblastoma.

Tompa M, Kalovits F, Nagy A, Kalman B Neuromolecular Med. 2018; 20(4):437-451.

PMID: 30259273 DOI: 10.1007/s12017-018-8514-x.

Host mediated inflammatory influence on glioblastoma multiforme recurrence following high-dose ionizing radiation.

McDonald J, Gao X, Steber C, Lee Breed J, Pollock C, Ma L PLoS One. 2017; 12(5):e0178155.

PMID: 28542439 PMC: 5439715. DOI: 10.1371/journal.pone.0178155.

Multiscale Modeling of Glioblastoma Suggests that the Partial Disruption of Vessel/Cancer Stem Cell Crosstalk Can Promote Tumor Regression Without Increasing Invasiveness.

Yan H, Romero-Lopez M, Frieboes H, Hughes C, Lowengrub J IEEE Trans Biomed Eng. 2016; 64(3):538-548.

PMID: 27723576 PMC: 5501302. DOI: 10.1109/TBME.2016.2615566.

Radiation-Induced Reprogramming of Pre-Senescent Mammary Epithelial Cells Enriches Putative CD44(+)/CD24(-/low) Stem Cell Phenotype.

Gao X, Sishc B, Nelson C, Hahnfeldt P, Bailey S, Hlatky L Front Oncol. 2016; 6:138.

PMID: 27379202 PMC: 4905979. DOI: 10.3389/fonc.2016.00138.

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