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The migration of cells in multicell tumor spheroids

McElwain, D. L. S., Pettet, G. J., Please, C. P., & Tindall, M. J. (2001) The migration of cells in multicell tumor spheroids. Bulletin of Mathematical Biology, 63(2), pp. 231-257.

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Abstract

A mathematical model is proposed to explain the observed internalization of microspheres and3H-thymidine labelled cells in steady-state multicellular spheroids. The model uses the conventional ideas of nutrient diffusion and consumption by the cells. In addition, a very simple model of the progress of the cells through the cell cycle is considered. Cells are divided into two classes, those proliferating (being in G1, S,G2 or M phases) and those that are quiescent (being in G0). Furthermore, the two categories are presumed to have different chemotactic responses to the nutrient gradient. The model accounts for the spatial and temporal variations in the cell categories together with mitosis, conversion between categories and cell death. Numerical solutions demonstrate that the model predicts the behavior similar to existing models but has some novel effects. It allows for spheroids to approach a steady-state size in a non-monotonic manner, it predicts self-sorting of the cell classes to produce a thin layer of rapidly proliferating cells near the outer surface and significant numbers of cells within the spheroid stalled in a proliferating state. The model predicts that overall tumor growth is not only determined by proliferation rates but also by the ability of cells to convert readily between the classes. Moreover, the steady-state structure of the spheroid indicates that if the outer layers are removed then the tumor grows quickly by recruiting cells stalled in a proliferating state. Questions are raised about the chemotactic response of cells in differing phases and to the dependency of cell cycle rates to nutrient levels.

Impact and interest:

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86 citations in Web of Science®

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ID Code: 8726
Item Type: Journal Article
Additional Information: For more information, please refer to the journal’s website (see hypertext link) or contact the author. Author contact details: g.pettet@qut.edu.au
DOI: 10.1006/bulm.2000.0217
ISSN: 1522-9602
Subjects: Australian and New Zealand Standard Research Classification > MATHEMATICAL SCIENCES (010000)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Mathematical Sciences
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Past > Schools > Mathematical Sciences
Copyright Owner: Copyright 2001 Springer
Copyright Statement: The original publication is available at SpringerLink http://www.springerlink.com
Deposited On: 06 Aug 2007
Last Modified: 18 Jun 2012 08:41

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