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

S. R. McDougall; M. A.J. Chaplain; A. Stéphanou; A. R.A. Anderson

Mathematical Modelling of Natural Phenomena (2010)

  • Volume: 5, Issue: 1, page 163-202
  • ISSN: 0973-5348

Abstract

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Over the past decade or so, there have been a large number of modelling approaches aimed at elucidating the most important mechanisms affecting the formation of new capillaries from parent blood vessels — a process known as angiogenesis. Most studies have focussed upon the way in which capillary sprouts are initiated and migrate in response to diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the contexts of solid tumour growth and wound healing. However, relatively few studies have examined the important role played by blood perfusion during angiogenesis and fewer still have explored the ways in which a dynamically evolving vascular bed architecture can affect the distribution of flow within it. From the perspective of solid tumour growth and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of some benefit to understand this coupling between vascular structure and perfusion more fully. 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 during vessel maturation is considered in order to study the effects of different anti-vascular and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a prime target for new vascular disrupting agents (VDAs) currently in clinical trials. However, different compounds attack different components of the vascular network and the implications of targeting only certain elements of the capillary bed are not immediately clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular drugs are re-examined by using an extended model that includes an interdependency between vessel remodelling potential and local pericyte density. Two- and three-dimensional simulation results are presented and suggest that it may be possible to identify a VDA-specific “plasticity window” (a time period corresponding to low pericyte density), within which a given VDA would be most effective.

How to cite

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McDougall, S. R., et al. "Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents." Mathematical Modelling of Natural Phenomena 5.1 (2010): 163-202. <http://eudml.org/doc/197629>.

@article{McDougall2010,
abstract = {Over the past decade or so, there have been a large number of modelling approaches aimed at elucidating the most important mechanisms affecting the formation of new capillaries from parent blood vessels — a process known as angiogenesis. Most studies have focussed upon the way in which capillary sprouts are initiated and migrate in response to diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the contexts of solid tumour growth and wound healing. However, relatively few studies have examined the important role played by blood perfusion during angiogenesis and fewer still have explored the ways in which a dynamically evolving vascular bed architecture can affect the distribution of flow within it. From the perspective of solid tumour growth and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of some benefit to understand this coupling between vascular structure and perfusion more fully. 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 during vessel maturation is considered in order to study the effects of different anti-vascular and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a prime target for new vascular disrupting agents (VDAs) currently in clinical trials. However, different compounds attack different components of the vascular network and the implications of targeting only certain elements of the capillary bed are not immediately clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular drugs are re-examined by using an extended model that includes an interdependency between vessel remodelling potential and local pericyte density. Two- and three-dimensional simulation results are presented and suggest that it may be possible to identify a VDA-specific “plasticity window” (a time period corresponding to low pericyte density), within which a given VDA would be most effective.},
author = {McDougall, S. R., Chaplain, M. A.J., Stéphanou, A., Anderson, A. R.A.},
journal = {Mathematical Modelling of Natural Phenomena},
keywords = {tumour-induced angiogenesis; blood vessel networks; pericytes; chemotherapeutic; anti-angiogenic; anti-vascular treatment protocols},
language = {eng},
month = {2},
number = {1},
pages = {163-202},
publisher = {EDP Sciences},
title = {Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents},
url = {http://eudml.org/doc/197629},
volume = {5},
year = {2010},
}

TY - JOUR
AU - McDougall, S. R.
AU - Chaplain, M. A.J.
AU - Stéphanou, A.
AU - Anderson, A. R.A.
TI - Modelling the Impact of Pericyte Migration and Coverage of Vessels on the Efficacy of Vascular Disrupting Agents
JO - Mathematical Modelling of Natural Phenomena
DA - 2010/2//
PB - EDP Sciences
VL - 5
IS - 1
SP - 163
EP - 202
AB - Over the past decade or so, there have been a large number of modelling approaches aimed at elucidating the most important mechanisms affecting the formation of new capillaries from parent blood vessels — a process known as angiogenesis. Most studies have focussed upon the way in which capillary sprouts are initiated and migrate in response to diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the contexts of solid tumour growth and wound healing. However, relatively few studies have examined the important role played by blood perfusion during angiogenesis and fewer still have explored the ways in which a dynamically evolving vascular bed architecture can affect the distribution of flow within it. From the perspective of solid tumour growth and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of some benefit to understand this coupling between vascular structure and perfusion more fully. 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 during vessel maturation is considered in order to study the effects of different anti-vascular and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a prime target for new vascular disrupting agents (VDAs) currently in clinical trials. However, different compounds attack different components of the vascular network and the implications of targeting only certain elements of the capillary bed are not immediately clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular drugs are re-examined by using an extended model that includes an interdependency between vessel remodelling potential and local pericyte density. Two- and three-dimensional simulation results are presented and suggest that it may be possible to identify a VDA-specific “plasticity window” (a time period corresponding to low pericyte density), within which a given VDA would be most effective.
LA - eng
KW - tumour-induced angiogenesis; blood vessel networks; pericytes; chemotherapeutic; anti-angiogenic; anti-vascular treatment protocols
UR - http://eudml.org/doc/197629
ER -

References

top
  1. T. Alarcon, H.M. Byrne P.K. Maini. A cellular automaton model for tumour growth in inhomogeneous environment. J. Theor. Biol., 225 (2003), 257–274 
  2. A.R.A. Anderson M.A.J. Chaplain. Continuous and discrete mathematical models of tumor-induced angiogenesis. Bull. Math. Biol., 60 (1998), 857–899 
  3. A. Armulik, A. Abramsson, C. Betsholtz. (2005). Endothelial/pericyte interactions. Circulation Research, 97 (2005), 512–523 
  4. D.H. Ausprunk J. Folkman. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumour angiogenesis. Microvasc. Res., 14 (1977), 53–65 
  5. R.G. Bagley. Pericytes from human non-small cell lung carcinomas: An attractive target for anti-angiogenic therapy. Microvascular Res., 71 (2006), 163–174 
  6. J.W. Baish, Y. Gazit, D.A. Berk, M. Nozue, L.T. Baxter R.K. Jain. Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model. Microvasc. Res., 51 (1996), 327–346 
  7. L.E. Benjamin, I. Hemo E. Keshet. 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 
  8. D. Bray. Cell Movements. New-York: Garland Publishing, 1992.  
  9. R.A. Brekken, P.E. Thorpe. Vascular endothelial growth factor and vascular targeting of solid tumors. 21 (2001), 4221–4229.  
  10. C.F. Chantrain, P. Henriet, S. Jodele, H. Emonard, O. Feron, P.J. Courtoy, Y.A. DeClerck, E. Marbaix (2006). Mechanisms of pericyte recruitment in tumour angiogenesis: A new role for metalloproteinases. European J. Cancer, 42 (2006), 310–318 
  11. M.A.J. Chaplain G. Lolas. 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 
  12. M. Ciofalo, M.W. Collins, T.R. Hennessy. “Microhydrodynamics phenomena in the circulation.” In: Nanoscale fluid dynamics in physiological processes: A review study. WIT Press, Southampton, 1999, pp 219–236.  
  13. G.E. Davis, K.A. Pintar Allen, R. Salazar S.A. Maxwell. 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 
  14. A.W. El-Kareh T.W. SecombTheoretical models for drug delivery to solid tumours. Crit. Rev. Biomed. Eng., 25 (1997), 503–571 
  15. J. Folkman M. Klagsbrun. Angiogenic factors. Science, 235 (1987), 442–447 
  16. Y.C. Fung. Biomechanics. Springer-Verlag, New-York, 1993.  
  17. M.S. Gee, W.N. Procopio, S. Makonnen, M.D. Feldman, N.W. Yeilding W.M.F. Lee. Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. Am. J. Path., 162 (2003), 183–193 
  18. R. Gödde H. Kurz. Structural and biophysical simulation of angiogenesis and vascular remodeling. Developmental Dynamics, 220 (2001), 387–401 
  19. M. Hidalgo S.G. Eckkhardt. Development of matrix metalloproteinase inhibitors in cancer therapy. Journal of the National Cancer Institute, 93 (2001), 178–193 
  20. S. Hughes, T. Gardiner, P. Hu, L. Baxter, E. Rosinova T. Chan-Ling. Altered pericyte-endothelial relations in the rat retina during aging: Implications for vessel stability. Neurobiology of Aging, 27 (2006), 1838–1847 
  21. Y. Izumi. Tumour biology: herceptin acts as an antiangiogenic cocktail. Nature416 (2002), 279–280.  
  22. T.L. Jackson, S.R. Lubkin, J.D. Murray. Theoretical analysis of conjugate localization in two-step cancer chemotherapy. J. Math. Biol.39 (1999), 353–376.  
  23. R.K. Jain. (2003)Molecular regulation of vessel maturation. Nat. Med., 9 (2003), 685–93 
  24. A. Kamiya, R. Bukhari, T. Togawa. Adaptive regulation of wall shear stress optimizing vascular tree function. Bull. Math. Biology.46 (1984), 127–137.  
  25. G.S. Krenz C.A. Dawson. Vessel distensibility and flow distribution in vascular trees. J. Math. Biol., 44 (2002), 360–374 
  26. C.C. Kumar. Targeting integrins αvβ3 and αvβ5 for blocking tumour-induced angiogenesis. Adv. Exp. Med. Biol., 476 (2000), 169–180 
  27. H.A. Levine, S. Pamuk, B.D. Sleeman M. Nielsen-Hamilton. Mathematical modeling of the capillary formation and development in tumor angiogenesis: penetration into the stroma. Bull. Math. Biol., 63 (2001), 801–863 
  28. S.R. McDougall, A.R.A. Anderson, M.A.J. Chaplain J.A. Sherratt. Mathematical modelling of flow through vascular networks: implications for tumour-induced angiogenesis and chemotherapy strategies. Bull. Math. Biol., 64 (2002), 673–702 
  29. S.R. McDougall, A.R.A. Anderson M.A.J. Chaplain. Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies. J. Theor. Biol., 241 (2006), 564–589 
  30. J.A. Madri, B.M. Pratt. Endothelial cell-matrix interactions: in vitro models of angiogenesis. J. Histochem. Cytochem.34 (1986), 85–91.  
  31. M.R. Mancusoet al.Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J. Clin. Investigation, 116 (2006), 2610–2621 
  32. S. Morikawa, P. Baluk, T. Kaidoh, A. Haskell, R.K. Jain D.M. McDonald. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am. J. Path., 160 (2002), 985–1000 
  33. L.L. Munn. Aberrant vascular architecture in tumors and its importance in drug-based therapies. Drug Discovery Today, 8 (2003), 396–403 
  34. N. Paweletz, M. Knierim. Tumor-related angiogenesis. Crit. Rev. Oncol. Hematol.9 (1989), 197–242.  
  35. A.R. Pries, T.W. Secomb P. Gaehtgens. Biophysical aspects of blood flow in the microvasculature. Cardiovasc. Res., 32 (1996), 654–667 
  36. A.R. Pries, T.W. Secomb P. Gaehtgens. Structural adaptation and stability of microvascular networks: theory and simulation. Am. J. Physiol., 275 (1998), H349–H360 
  37. A.R. Pries, B. Reglin T.W. Secomb. Structural adaptation of microvascular networks: functional roles of adaptive responses. Am. J. Physiol., 281 (2001), H1015–H1025 
  38. A.R. Pries, B. Reglin T.W. Secomb. Structural adaptation of vascular networks: role of the pressure response. Hypertension, 38 (2001), 1476–1479 
  39. A. Quarteroni, M. Tuveri A. Veneziani. Computational vascular fluid dynamics: problems, models and methods. Comput. Visual. Sci., 2 (2000), 163–197 
  40. S. Rafil. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?Nature Reviews Cancer, 2 (2002), 826–835.  
  41. C. Rouget. Memoire sur le developpement, la structure et les proprietes physiologiques des capillaires sanguins et lymphatiques. Arch. Physiol. Norm. Pathol., 5 (1873), 603–663 
  42. 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.  
  43. G.I. Schoefl. Studies of inflammation III. Growing capillaries: Their structure and permeability. Virchows Arch. Path. Anat., 337 (1963), 97–141 
  44. M.M. Sholley, G.P. Ferguson, H.R. Seibel, J.L. Montour J.D. Wilson. Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells. Lab. Invest., 51 (1984), 624–634 
  45. A. Stéphanou, S.R. McDougall, A.R.A. Anderson M.A.J. Chaplain. 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 
  46. A. Stéphanou, S.R. McDougall, A.R.A. Anderson M.A.J. Chaplain. Mathematical modelling of the influence of blood rheological properties upon adaptive tumour-induced angiogenesis. Math. Comp. Model., 44 (2005), 96–123 
  47. M.D. Sternlicht Z. Werb. How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell Dev. Biol., 17 (2001), 463–516 
  48. G.M. Tozer, C. Kanthou B.C. Baguley. Disrupting tumour blood vessels. Nature Reviews Cancer, 5 (2005), 423–433 
  49. L. Yan, M.A. Moses, S. Huang, D. Ingber (2000) Adhesion-dependent control of matrix metalloproteinase-2 activation in human capillary endothelial cells. J. Cell Sci., 113 (2000), 3979–3987.  

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