The migration of cells in multicell tumor spheroids
 G. J. Pettet,
 C. P. Please,
 M. J. Tindall,
 D. L. S. McElwain
 … show all 4 hide
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A mathematical model is proposed to explain the observed internalization of microspheres and ^{3}Hthymidine labelled cells in steadystate 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 G _{1}, S, G _{2} or M phases) and those that are quiescent (being in G _{0}). 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 steadystate size in a nonmonotonic manner, it predicts selfsorting 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 steadystate 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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 Title
 The migration of cells in multicell tumor spheroids
 Journal

Bulletin of Mathematical Biology
Volume 63, Issue 2 , pp 231257
 Cover Date
 20010301
 DOI
 10.1006/bulm.2000.0217
 Print ISSN
 00928240
 Online ISSN
 15229602
 Publisher
 SpringerVerlag
 Additional Links
 Topics
 Industry Sectors
 Authors

 G. J. Pettet ^{(1)}
 C. P. Please ^{(2)}
 M. J. Tindall ^{(2)}
 D. L. S. McElwain ^{(1)}
 Author Affiliations

 1. CiSSaIM, School of Mathematical Sciences, Queensland University of Technology, GPO Box 2434, Brisbane, QLD, 4001, Australia
 2. Faculty of Mathematical Studies, The University of Southampton, Southampton, SO17 1BJ, UK