2013, 10(1): 167-184. doi: 10.3934/mbe.2013.10.167

A structural model of the VEGF signalling pathway: Emergence of robustness and redundancy properties

1. 

INRIA, Project-team NUMED, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69007 Lyon Cedex 07, France, France, France, France

Received  July 2012 Revised  September 2012 Published  December 2012

The vascular endothelial growth factor (VEGF) is known as one of the main promoter of angiogenesis - the process of blood vessel formation. Angiogenesis has been recognized as a key stage for cancer development and metastasis. In this paper, we propose a structural model of the main molecular pathways involved in the endothelial cells response to VEGF stimuli. The model, built on qualitative information from knowledge databases, is composed of 38 ordinary differential equations with 78 parameters and focuses on the signalling driving endothelial cell proliferation, migration and resistance to apoptosis. Following a VEGF stimulus, the model predicts an increase of proliferation and migration capability, and a decrease in the apoptosis activity. Model simulations and sensitivity analysis highlight the emergence of robustness and redundancy properties of the pathway. If further calibrated and validated, this model could serve as tool to analyse and formulate new hypothesis on th e VEGF signalling cascade and its role in cancer development and treatment.
Citation: Floriane Lignet, Vincent Calvez, Emmanuel Grenier, Benjamin Ribba. A structural model of the VEGF signalling pathway: Emergence of robustness and redundancy properties. Mathematical Biosciences & Engineering, 2013, 10 (1) : 167-184. doi: 10.3934/mbe.2013.10.167
References:
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show all references

References:
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[11]

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[12]

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[13]

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[14]

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[15]

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[16]

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[17]

S. Faivre, G. Demetri, W. Sargent and E. Raymond, Molecular basis for sunitinib efficacy and future clinical development,, Nature Reviews Drug Discovery, 6 (2007), 734.  doi: 10.1038/nrd2380.  Google Scholar

[18]

N. Ferrara, VEGF and the quest for tumour angiogenesis factors,, Nature Reviews Cancer, 2 (2002), 795.  doi: 10.1038/nrc909.  Google Scholar

[19]

N. Ferrara, Vascular endothelial growth factor: basic science and clinical progress,, Endocrine Reviews, 25 (2004), 581.  doi: 10.1210/er.2003-0027.  Google Scholar

[20]

N. Ferrara, K. J. Hillan and W. Novotny, Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy,, Biochemical and Biophysical Research Communications, 333 (2005), 326.  doi: 10.1016/j.bbrc.2005.05.132.  Google Scholar

[21]

J. Folkman, Tumor angiogenesis factor,, Cancer Research, 34 (1974).   Google Scholar

[22]

J. Folkman, New perspectives in clinical oncology from angiogenesis research,, European Journal of Cancer (Oxford, 32 (1996).   Google Scholar

[23]

F. M. Gabhann and A. S. Popel, Systems biology of vascular endothelial growth factors,, Microcirculation, 15 (2008), 715.  doi: 10.1080/10739680802095964.  Google Scholar

[24]

G. Gasparini, R. Longo, M. Fanelli and B. A. Teicher, Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions,, Journal of Clinical Oncology, 23 (2005), 1295.  doi: 10.1200/JCO.2005.10.022.  Google Scholar

[25]

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[26]

F. Graner and J. A. Glazier, Simulation of biological cell sorting using a two-dimensional extended Potts model,, Physical Review Letters, 69 (1992), 2013.  doi: 10.1103/PhysRevLett.69.2013.  Google Scholar

[27]

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[29]

C. Y. Huang and J. E. Ferrell, Ultrasensitivity in the mitogen-activated protein kinase cascade,, Proceedings of the National Academy of Sciences, 93 (1996), 10078.  doi: 10.1073/pnas.93.19.10078.  Google Scholar

[30]

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[33]

H. Kitano, Computational systems biology,, Nature, 420 (2002), 206.  doi: 10.1038/nature01254.  Google Scholar

[34]

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