Dynamic modeling of genes controlling cancer stem cell proliferation.

Zhong Wang,Yao Li,Ningtao Wang,Jianxin Wang,Jingyuan Liu,Yaqun Wang,Rongling Wu,Runze Li

doi:10.3389/fgene.2012.00084

Abstract

The growing evidence that cancer originates from stem cells (SC) holds a great promise to eliminate this disease by designing specific drug therapies for removing cancer SC. Translation of this knowledge into predictive tests for the clinic is hampered due to the lack of methods to discriminate cancer SC from non-cancer SC. Here, we address this issue by describing a conceptual strategy for identifying the genetic origins of cancer SC. The strategy incorporates a high-dimensional group of differential equations that characterizes the proliferation, differentiation, and reprogramming of cancer SC in a dynamic cellular and molecular system. The deployment of robust mathematical models will help uncover and explain many still unknown aspects of cell behavior, tissue function, and network organization related to the formation and division of cancer SC. The statistical method developed allows biologically meaningful hypotheses about the genetic control mechanisms of carcinogenesis and metastasis to be tested in a quantitative manner.

Highlights

Human cancers grow from stem cells (SC) in the way that healthy organs do (Dick, 2003; Dontu et al, 2003; Alison, 2005; Brown et al, 2007; Lobo et al, 2007; Baumann et al, 2008; Visvader and Lindeman, 2008)
We review several key aspects of the genetic architecture of cancer SC, which can embedded into systems mapping (2). ωj|i can be expressed at the individual locus level or haplotype level (Liu et al, 2004), and can be used to model genetic main effects or epistatic interactions that occur within and between genomes (Li and Wu, 2009). ωj|i can consider genetic imprinting and epigenetic effects by incorporating the parental information of mapping individuals
We argue that the integration of functional and systems mapping (Wu and Lin, 2006; Li and Wu, 2010; Wu et al, 2011) with mathematical models for describing the origin and proliferation of cancer SC (Colijn and Mackey, 2005a,b; Ganguly and Puri, 2006; Enderling et al, 2007; Adimy et al, 2008; Michor, 2008; Piotrowska et al, 2008) may shed light on a better understanding of cancer genetics

Summary

Dynamic modeling of genes controlling cancer stem cell proliferation

Zhong Wang 1, Jingyuan Liu, Jianxin Wang 1, Yaqun Wang 2, Ningtao Wang 2, Yao Li 3, Runze Li 1,2 and Rongling Wu1,2*. The growing evidence that cancer originates from stem cells (SC) holds a great promise to eliminate this disease by designing specific drug therapies for removing cancer SC. Translation of this knowledge into predictive tests for the clinic is hampered due to the lack of methods to discriminate cancer SC from non-cancer SC. We address this issue by describing a conceptual strategy for identifying the genetic origins of cancer SC.

INTRODUCTION

Mature cell compartment

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DISCUSSION