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Modelling the Impact of Pericyte Migration and Coverage ofVessels on the Efficacy of Vascular Disrupting Agents

Published online by Cambridge University Press:  03 February 2010

S. R. McDougall ,
M. A.J. Chaplain ,
A. Stéphanou  and
A. R.A. Anderson
S. R. McDougall
Affiliation:
Heriot-Watt University, Edinburgh, EH14 4AS, Scotland
M. A.J. Chaplain*
Affiliation:
Division of Mathematics, University of Dundee, Dundee, DD1 4HN, Scotland
A. Stéphanou
Affiliation:
Faculté de Médecine de Grenoble, 38706 La Tronche Cedex, France.
A. R.A. Anderson
Affiliation:
Division of Mathematics, University of Dundee, Dundee, DD1 4HN, Scotland
*
*Corresponding author. E-mail:chaplain@maths.dundee.ac.uk
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Abstract

Over the past decade or so, there have been a large number of modelling approaches aimedat elucidating the most important mechanisms affecting the formation of new capillariesfrom parent blood vessels — a process known as angiogenesis. Most studies have focussedupon the way in which capillary sprouts are initiated and migrate in response todiffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in thecontexts of solid tumour growth and wound healing. However, relatively few studies haveexamined the important role played by blood perfusion during angiogenesis and fewer stillhave explored the ways in which a dynamically evolving vascular bed architecture canaffect the distribution of flow within it. From the perspective of solid tumour growthand, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be ofsome benefit to understand this coupling between vascular structure and perfusion morefully. This paper focuses on the implications of such a coupling upon chemotherapeutic,anti-angiogenic, and anti-vascular treatments.

In an extension to previous work by the authors, the issue of pericyte recruitment duringvessel maturation is considered in order to study the effects of different anti-vascularand anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are aprime target for new vascular disrupting agents (VDAs) currently in clinical trials.However, different compounds attack different components of the vascular network and theimplications of targeting only certain elements of the capillary bed are not immediatelyclear. In light of these uncertainties, the effects of anti-angiogenic and anti-vasculardrugs are re-examined by using an extended model that includes an interdependency betweenvessel remodelling potential and local pericyte density. Two- and three-dimensionalsimulation results are presented and suggest that it may be possible to identify aVDA-specific “plasticity window” (a time period corresponding to low pericyte density),within which a given VDA would be most effective.

Keywords

tumour-induced angiogenesisblood vessel networkspericyteschemotherapeuticanti-angiogenicanti-vascular treatment protocols
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 5 , Issue 1: Cell migration , 2010 , pp. 163 - 202
Copyright
© EDP Sciences, 2010

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