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...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2013
|
Online Access: | https://hdl.handle.net/10356/96024 http://hdl.handle.net/10220/10119 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-96024 |
---|---|
record_format |
dspace |
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 |
_version_ |
1681056797261037568 |