Journal
JOURNAL OF THE ROYAL SOCIETY INTERFACE
Volume 4, Issue 13, Pages 283-304Publisher
ROYAL SOC
DOI: 10.1098/rsif.2006.0170
Keywords
angiogenesis; vascular endothelial growth factor; receptor tyrosine kinase; oligomerization; endocytosis; master equation
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Funding
- Engineering and Physical Sciences Research Council [GR/S09067/01] Funding Source: researchfish
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We present an analysis of a stochastic model of the vascular endothelial growth factor (VEGF) receptor. This analysis addresses the contribution of ligand-binding-induced oligomerization, activation of src-homology 2 domain-carrying kinases and receptor internalization in the overall behaviour of the VEGF/VEGF receptor (VEGFR,) system. The analysis is based upon a generalization of a Wentzel-Kramers-Brillouin (WKB) approximation of the solution of the corresponding master equation. We predict that tumour-mediated overexpression of VEGFRs in the endothelial cells (ECs) of tumour-engulfed vessels leads to an increased sensitivity of the ECs to low concentrations of VEGF, thus endowing the tumour with increased resistance to anti-angiogenic treatment.
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