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Modeling the Cancer Stem Cell Hypothesis

Published online by Cambridge University Press:  28 April 2010

C. Calmelet ,
A. Prokop ,
J. Mensah ,
L. J. McCawley  and
P. S. Crooke
C. Calmelet*
Affiliation:
Department of Mathematics and Statistics, California State University Chico
A. Prokop
Affiliation:
Department of Chemical Engineering ,Vanderbilt University
J. Mensah
Affiliation:
Department of Chemistry, Tennessee State University
L. J. McCawley
Affiliation:
Department of Cancer Biology, Vanderbilt University
P. S. Crooke
Affiliation:
Department of Mathematics, Vanderbilt University
*
*Corresponding author. E-mail:ccalmelet@csuchico.edu
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Abstract

Solid tumors and hematological cancers contain small population of tumor cells that arebelieved to play a critical role in the development and progression of the disease. Thesecells, named Cancer Stem Cells (CSCs), have been found in leukemia, myeloma, breast,prostate, pancreas, colon, brain and lung cancers. It is also thought that CSCs drive themetastatic spread of cancer. The CSC compartment features a specific and phenotypicallydefined cell population characterized with self-renewal (through mutations), quiescence orslow cycling, overexpression of anti-apoptotic proteins, multidrug resistance and impaireddifferentiation. CSCs show resistance to a number of conventional therapies, and it isbelieved that this explains why it is difficult to completely eradicate the disease andwhy recurrence is an ever-present threat. A hierarchical phenomenological model isproposed based on eight compartments following the stem cell lineage at the normal andcancer cell levels. As an empirical test, the tumor grading and progression, typicallycollected in the pathologic lab, is used to correlate the outcome of this model with thetumor development stages. In addition, the model is able to quantitatively account for thetemporal development of the population of observed cell types. Two types of therapeutictreatment models are considered, with dose-density chemotherapy (a pulsatile scenario) aswell as continuous, metronomic delivery. The drug hit is considered at the stem cellprogenitor and early differentiated specialized cell levels for both normal and cancercells, while the quiescent stem cell and fully differentiated compartments are consideredfavorable outcome for cancer treatment. Circulating progenitors are neglected in thisanalysis. The model provides a number of experimentally testable predictions. The relativeimportance of the cell kill and survival is demonstrated through a deterministicparametric study. The significance of the stem cell compartment is underlined based onthis simulation study. This predictive mathematical model for cancer stem cell hypothesisis used to understand tumor responses to chemotherapeutic agents and judge theefficacy.

Keywords

Stem cellmathematical modelhypothesiscancer therapy
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 5 , Issue 3: Mathematical modeling in the medical sciences , 2010 , pp. 40 - 62
Copyright
© EDP Sciences, 2010

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