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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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References

Alarcon, T., Byrne, H.M. Maini, P.K.. A cellular automaton model for tumour growth in inhomogeneous environment . J. Theor. Biol., 225 (2003), 257–274 CrossRefGoogle ScholarPubMed
Anderson, A.R.A. Chaplain, M.A.J.. Continuous and discrete mathematical models of tumor-induced angiogenesis . Bull. Math. Biol., 60 (1998), 857–899 CrossRefGoogle ScholarPubMed
Armulik, A., Abramsson, A., Betsholtz, C.. (2005). Endothelial/pericyte interactions . Circulation Research, 97 (2005), 512–523 CrossRefGoogle ScholarPubMed
Ausprunk, D.H. Folkman, J.. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumour angiogenesis . Microvasc. Res., 14 (1977), 53–65 CrossRefGoogle Scholar
Bagley, R.G.. Pericytes from human non-small cell lung carcinomas: An attractive target for anti-angiogenic therapy . Microvascular Res., 71 (2006), 163–174 CrossRefGoogle ScholarPubMed
Baish, J.W., Gazit, Y., Berk, D.A., Nozue, M., Baxter, L.T. Jain, R.K.. Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model . Microvasc. Res., 51 (1996), 327–346 CrossRefGoogle ScholarPubMed
Benjamin, L.E., Hemo, I. Keshet, E.. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF . Development, 125 (1998), 1591–1598 Google ScholarPubMed
D. Bray. Cell Movements. New-York: Garland Publishing, 1992.
Brekken, R.A., Thorpe, P.E.. Vascular endothelial growth factor and vascular targeting of solid tumors . 21 (2001), 4221–4229. Google ScholarPubMed
Chantrain, C.F., Henriet, P., Jodele, S., Emonard, H., Feron, O., Courtoy, P.J., DeClerck, Y.A., Marbaix, E. (2006). Mechanisms of pericyte recruitment in tumour angiogenesis: A new role for metalloproteinases . European J. Cancer, 42 (2006), 310–318 CrossRefGoogle ScholarPubMed
Chaplain, M.A.J. Lolas, G.. Mathematical modelling of cancer cell invasion of tissue: The role of the urokinase plasminogen activator system . Math. Mod. Meth. Appl. Sci., 11 (2005), 1685–1734 CrossRefGoogle Scholar
Ciofalo, M., Collins, M.W., Hennessy, T.R.. “Microhydrodynamics phenomena in the circulation.” In: Nanoscale fluid dynamics in physiological processes: A review study. WIT Press, Southampton, 1999, pp 219–236. Google Scholar
Davis, G.E., Pintar Allen, K.A. , Salazar, R. Maxwell, S.A.. Matrix metalloproteinase-1 and –9 activation by plasmin regulates a novel endothelial cell-mediated mechanism of collagen gel contraction and capillary tube regression in three-dimensional collagen matrices . J. Cell Sci., 114 (2000), 917–930 Google ScholarPubMed
El-Kareh, A.W. Secomb, T.W. Theoretical models for drug delivery to solid tumours . Crit. Rev. Biomed. Eng., 25 (1997), 503–571 CrossRefGoogle Scholar
Folkman, J. Klagsbrun, M.. Angiogenic factors . Science, 235 (1987), 442–447 CrossRefGoogle ScholarPubMed
Y.C. Fung. Biomechanics. Springer-Verlag, New-York, 1993.
Gee, M.S., Procopio, W.N., Makonnen, S., Feldman, M.D., Yeilding, N.W. Lee, W.M.F.. Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy . Am. J. Path., 162 (2003), 183–193 CrossRefGoogle Scholar
Gödde, R. Kurz, H.. Structural and biophysical simulation of angiogenesis and vascular remodeling . Developmental Dynamics, 220 (2001), 387–401 CrossRefGoogle ScholarPubMed
Hidalgo, M. Eckkhardt, S.G.. Development of matrix metalloproteinase inhibitors in cancer therapy . Journal of the National Cancer Institute, 93 (2001), 178–193 CrossRefGoogle ScholarPubMed
Hughes, S., Gardiner, T., Hu, P., Baxter, L., Rosinova, E. Chan-Ling, T.. Altered pericyte-endothelial relations in the rat retina during aging: Implications for vessel stability . Neurobiology of Aging, 27 (2006), 1838–1847 CrossRefGoogle Scholar
Izumi, Y.. Tumour biology: herceptin acts as an antiangiogenic cocktail . Nature 416 (2002), 279–280. CrossRefGoogle ScholarPubMed
Jackson, T.L., Lubkin, S.R., Murray, J.D.. Theoretical analysis of conjugate localization in two-step cancer chemotherapy . J. Math. Biol. 39 (1999), 353–376. CrossRefGoogle ScholarPubMed
Jain, R.K.. (2003) Molecular regulation of vessel maturation . Nat. Med., 9 (2003), 685–93 CrossRefGoogle ScholarPubMed
Kamiya, A., Bukhari, R., Togawa, T.. Adaptive regulation of wall shear stress optimizing vascular tree function . Bull. Math. Biology. 46 (1984), 127–137. CrossRefGoogle ScholarPubMed
Krenz, G.S. Dawson, C.A.. Vessel distensibility and flow distribution in vascular trees . J. Math. Biol., 44 (2002), 360–374 CrossRefGoogle Scholar
Kumar, C.C.. Targeting integrins α v β 3 and α v β 5 for blocking tumour-induced angiogenesis . Adv. Exp. Med. Biol., 476 (2000), 169–180 CrossRefGoogle Scholar
Levine, H.A., Pamuk, S., Sleeman, B.D. Nielsen-Hamilton, M.. Mathematical modeling of the capillary formation and development in tumor angiogenesis: penetration into the stroma . Bull. Math. Biol., 63 (2001), 801–863 CrossRefGoogle ScholarPubMed
McDougall, S.R., Anderson, A.R.A., Chaplain, M.A.J. Sherratt, J.A.. Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies . Bull. Math. Biol., 64 (2002), 673–702 CrossRefGoogle ScholarPubMed
McDougall, S.R., Anderson, A.R.A. Chaplain, M.A.J.. Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies . J. Theor. Biol., 241 (2006), 564–589 CrossRefGoogle ScholarPubMed
Madri, J.A., Pratt, B.M.. Endothelial cell-matrix interactions: in vitro models of angiogenesis . J. Histochem. Cytochem. 34 (1986), 85–91. CrossRefGoogle ScholarPubMed
Mancuso, M.R. et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition . J. Clin. Investigation, 116 (2006), 2610–2621 CrossRefGoogle ScholarPubMed
Morikawa, S., Baluk, P., Kaidoh, T., Haskell, A., Jain, R.K. McDonald, D.M.. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors . Am. J. Path., 160 (2002), 985–1000 CrossRefGoogle ScholarPubMed
Munn, L.L.. Aberrant vascular architecture in tumors and its importance in drug-based therapies . Drug Discovery Today, 8 (2003), 396–403 CrossRefGoogle Scholar
Paweletz, N., Knierim, M.. Tumor-related angiogenesis . Crit. Rev. Oncol. Hematol. 9 (1989), 197–242. CrossRefGoogle ScholarPubMed
Pries, A.R., Secomb, T.W. Gaehtgens, P.. Biophysical aspects of blood flow in the microvasculature . Cardiovasc. Res., 32 (1996), 654–667 CrossRefGoogle ScholarPubMed
Pries, A.R., Secomb, T.W. Gaehtgens, P.. Structural adaptation and stability of microvascular networks: theory and simulation . Am. J. Physiol., 275 (1998), H349–H360 Google Scholar
Pries, A.R., Reglin, B. Secomb, T.W.. Structural adaptation of microvascular networks: functional roles of adaptive responses . Am. J. Physiol., 281 (2001), H1015–H1025 Google ScholarPubMed
Pries, A.R., Reglin, B. Secomb, T.W.. Structural adaptation of vascular networks: role of the pressure response . Hypertension, 38 (2001), 1476–1479 CrossRefGoogle Scholar
Quarteroni, A., Tuveri, M. Veneziani, A.. Computational vascular fluid dynamics: problems, models and methods . Comput. Visual. Sci., 2 (2000), 163–197 CrossRefGoogle Scholar
Rafil, S.. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nature Reviews Cancer, 2 (2002), 826–835. Google Scholar
Rouget, C.. Memoire sur le developpement, la structure et les proprietes physiologiques des capillaires sanguins et lymphatiques . Arch. Physiol. Norm. Pathol., 5 (1873), 603–663 Google Scholar
T.W. Secomb. Mechanics of blood flow in the microcirculation. In “Biological Fluid Dynamics.” eds. C.P. Ellington and T.J. Pedley. Company of Biologists, Cambridge, 1995, pp. 305-321.
Schoefl, G.I.. Studies of inflammation III. Growing capillaries: Their structure and permeability . Virchows Arch. Path. Anat., 337 (1963), 97–141 CrossRefGoogle Scholar
Sholley, M.M., Ferguson, G.P., Seibel, H.R., Montour, J.L. Wilson, J.D.. Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells . Lab. Invest., 51 (1984), 624–634 Google Scholar
Stéphanou, A., McDougall, S.R., Anderson, A.R.A. Chaplain, M.A.J.. Mathematical modelling of flow in 2D and 3D vascular networks: applications to anti-angiogenic and chemotherapeutic drug strategies . Math. Comp. Model., 41 (2005), 1137–1156 CrossRefGoogle Scholar
Stéphanou, A., McDougall, S.R., Anderson, A.R.A. Chaplain, M.A.J.. Mathematical modelling of the influence of blood rheological properties upon adaptive tumour-induced angiogenesis . Math. Comp. Model., 44 (2005), 96–123 CrossRefGoogle Scholar
Sternlicht, M.D. Werb, Z.. How matrix metalloproteinases regulate cell behavior . Annu. Rev. Cell Dev. Biol., 17 (2001), 463–516 CrossRefGoogle ScholarPubMed
Tozer, G.M., Kanthou, C. Baguley, B.C.. Disrupting tumour blood vessels . Nature Reviews Cancer, 5 (2005), 423–433 CrossRefGoogle ScholarPubMed
Yan, L., Moses, M.A., Huang, S., Ingber, D. (2000) Adhesion-dependent control of matrix metalloproteinase-2 activation in human capillary endothelial cells . J. Cell Sci., 113 (2000), 3979–3987. Google Scholar