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

Andrea Sottoriva, Joost J C Verhoeff, Tijana Borovski, Shannon McWeeney, Lev Naumov, Jan Paul Medema, Peter M A Sloot, Louis Vermeulen

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)46-56
Number of pages11
JournalCancer Research
Volume70
Issue number1
DOIs
StatePublished - Jan 1 2010

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Neoplastic Stem Cells
Neoplasms
Population
Theoretical Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Sottoriva, A., Verhoeff, J. J. C., Borovski, T., McWeeney, S., Naumov, L., Medema, J. P., ... Vermeulen, L. (2010). Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity. Cancer Research, 70(1), 46-56. https://doi.org/10.1158/0008-5472.CAN-09-3663

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.

In: Cancer Research, Vol. 70, No. 1, 01.01.2010, p. 46-56.

Research output: Contribution to journalArticle

Sottoriva, A, Verhoeff, JJC, Borovski, T, McWeeney, S, Naumov, L, Medema, JP, Sloot, PMA & Vermeulen, L 2010, 'Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity', Cancer Research, vol. 70, no. 1, pp. 46-56. https://doi.org/10.1158/0008-5472.CAN-09-3663
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. In: Cancer Research. 2010 ; Vol. 70, No. 1. pp. 46-56.
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