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

Floriane Lignet; Vincent Calvez; Emmanuel Grenier; Benjamin Ribba

doi:10.3934/mbe.2013.10.167

Article Contents

2013, Volume 10, Issue 1: 167-184. Doi: 10.3934/mbe.2013.10.167

This issue Previous Article On optimal and suboptimal treatment strategies for a mathematical model of leukemia Next Article A therapy inactivating the tumor angiogenic factors

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

Received: July 2012

Revised: September 2012

Published: November 2012

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Abstract

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.

Keywords:

Systems biology,
networks,
kinetics in biochemical problems,
molecular reactions,
ordinary differential equations,
Vascular Endothelial Growth Factor (VEGF) signalling.

Mathematics Subject Classification: Primary: 92C42, 92C45, 92E20; Secondary: 65L99.

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