Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity

The recently developed concept of cancer stem cells (CSC) sheds new light on various aspects of tumor growth and progression. Here, we present a mathematical model of malignancies to investigate how a hierarchical organized cancer cell population affects the fundamental properties of solid malignanc...

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Main Authors: Sottoriva, Andrea, Verhoeff, Joost J. C., Borovski, Tijana, McWeeney, Shannon, Naumov, Lev, Medema, Jan Paul, Sloot, Peter M. A., Vermeulen, Louis
Other Authors: School of Computer Engineering
Format: Article
Language:English
Published: 2013
Online Access:https://hdl.handle.net/10356/96024
http://hdl.handle.net/10220/10119
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-960242020-05-28T07:17:20Z Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity Sottoriva, Andrea Verhoeff, Joost J. C. Borovski, Tijana McWeeney, Shannon Naumov, Lev Medema, Jan Paul Sloot, Peter M. A. Vermeulen, Louis School of Computer Engineering The recently developed concept of cancer stem cells (CSC) sheds new light on various aspects of tumor growth and progression. Here, we present a mathematical model of malignancies to investigate how a hierarchical organized cancer cell population affects the fundamental properties of solid malignancies. We establish that tumors modeled in a CSC context more faithfully resemble human malignancies and show invasive behavior, whereas tumors without a CSC hierarchy do not. These findings are corroborated by in vitro studies. In addition, we provide evidence that the CSC model is accompanied by highly altered evolutionary dynamics compared with the ones predicted to exist in a stochastic, nonhierarchical tumor model. Our main findings indicate that the CSC model allows for significantly higher tumor heterogeneity, which may affect therapy resistance. Moreover, we show that therapy which fails to target the CSC population is not only unsuccessful in curing the patient, but also promotes malignant features in the recurring tumor. These include rapid expansion, increased invasion, and enhanced heterogeneity. 2013-06-10T06:16:56Z 2019-12-06T19:24:37Z 2013-06-10T06:16:56Z 2019-12-06T19:24:37Z 2010 2010 Journal Article Sottoriva, A., Verhoeff, J. J. C., Borovski, T., McWeeney, S. K., Naumov, L., Medema, J. P., et al. (2010). Cancer Stem Cell Tumor Model Reveals Invasive Morphology and Increased Phenotypical Heterogeneity. Cancer Research, 70(1), 46-56. https://hdl.handle.net/10356/96024 http://hdl.handle.net/10220/10119 10.1158/0008-5472.CAN-09-3663 en Cancer Research © 2010 American Association for Cancer Research.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
description The recently developed concept of cancer stem cells (CSC) sheds new light on various aspects of tumor growth and progression. Here, we present a mathematical model of malignancies to investigate how a hierarchical organized cancer cell population affects the fundamental properties of solid malignancies. We establish that tumors modeled in a CSC context more faithfully resemble human malignancies and show invasive behavior, whereas tumors without a CSC hierarchy do not. These findings are corroborated by in vitro studies. In addition, we provide evidence that the CSC model is accompanied by highly altered evolutionary dynamics compared with the ones predicted to exist in a stochastic, nonhierarchical tumor model. Our main findings indicate that the CSC model allows for significantly higher tumor heterogeneity, which may affect therapy resistance. Moreover, we show that therapy which fails to target the CSC population is not only unsuccessful in curing the patient, but also promotes malignant features in the recurring tumor. These include rapid expansion, increased invasion, and enhanced heterogeneity.
author2 School of Computer Engineering
author_facet School of Computer Engineering
Sottoriva, Andrea
Verhoeff, Joost J. C.
Borovski, Tijana
McWeeney, Shannon
Naumov, Lev
Medema, Jan Paul
Sloot, Peter M. A.
Vermeulen, Louis
format Article
author Sottoriva, Andrea
Verhoeff, Joost J. C.
Borovski, Tijana
McWeeney, Shannon
Naumov, Lev
Medema, Jan Paul
Sloot, Peter M. A.
Vermeulen, Louis
spellingShingle Sottoriva, Andrea
Verhoeff, Joost J. C.
Borovski, Tijana
McWeeney, Shannon
Naumov, Lev
Medema, Jan Paul
Sloot, Peter M. A.
Vermeulen, Louis
Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
author_sort Sottoriva, Andrea
title Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
title_short Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
title_full Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
title_fullStr Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
title_full_unstemmed Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
title_sort cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity
publishDate 2013
url https://hdl.handle.net/10356/96024
http://hdl.handle.net/10220/10119
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