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The migration of cells in multicell tumour spheroids

The migration of cells in multicell tumour spheroids
The migration of cells in multicell tumour spheroids
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.
0092-8240
231-257
Pettet, G.J.
d06ce471-7346-4c0c-971d-591d4f4fd680
Please, C.P.
118dffe7-4b38-4787-a972-9feec535839e
Tindall, M.J.
c9bcfff9-902d-43f9-8d16-4ab49e73b789
McElwain, D.L.S.
2b1b25a5-d12f-41bd-bf1a-0f8b9afd65b6
Pettet, G.J.
d06ce471-7346-4c0c-971d-591d4f4fd680
Please, C.P.
118dffe7-4b38-4787-a972-9feec535839e
Tindall, M.J.
c9bcfff9-902d-43f9-8d16-4ab49e73b789
McElwain, D.L.S.
2b1b25a5-d12f-41bd-bf1a-0f8b9afd65b6

Pettet, G.J., Please, C.P., Tindall, M.J. and McElwain, D.L.S. (2001) The migration of cells in multicell tumour spheroids. Bulletin of Mathematical Biology, 63 (2), 231-257. (doi:10.1006/bulm.2000.0217).

Record type: Article

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.

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Published date: 2001

Identifiers

Local EPrints ID: 29252
URI: http://eprints.soton.ac.uk/id/eprint/29252
ISSN: 0092-8240
PURE UUID: 57fb39b3-0d80-40dc-9723-1766f614934c

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Date deposited: 10 May 2006
Last modified: 15 Mar 2024 07:30

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Contributors

Author: G.J. Pettet
Author: C.P. Please
Author: M.J. Tindall
Author: D.L.S. McElwain

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