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Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
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7 h2 T& W/ v$ aCancer Res. 2010 Jan 1;70(1):46-56
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Authors: Sottoriva A, Verhoeff JJ, Borovski T, McWeeney SK, Naumov L, Medema JP, Sloot PM, Vermeulen L
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4 i8 A2 O: _7 n! e9 a Therecently developed concept of cancer stem cells (CSC) sheds new lighton various aspects of tumor growth and progression. Here, we present amathematical model of malignancies to investigate how a hierarchicalorganized cancer cell population affects the fundamental properties ofsolid malignancies. We establish that tumors modeled in a CSC contextmore faithfully resemble human malignancies and show invasive behavior,whereas tumors without a CSC hierarchy do not. These findings arecorroborated by in vitro studies. In addition, we provide evidence thatthe CSC model is accompanied by highly altered evolutionary dynamicscompared with the ones predicted to exist in a stochastic,nonhierarchical tumor model. Our main findings indicate that the CSCmodel allows for significantly higher tumor heterogeneity, which mayaffect therapy resistance. Moreover, we show that therapy which failsto target the CSC population is not only unsuccessful in curing thepatient, but also promotes malignant features in the recurring tumor.These include rapid expansion, increased invasion, and enhancedheterogeneity.: P9 L: Q# {% K6 t( e
PMID: 20048071 [PubMed - in process] |
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发表于 2010-1-7 22:00
