Exploring the Extracellular Regulation of the Tumor Angiogenic Interaction Network Using a Systems Biology Model
Abstract
Tumor angiogenesis is regulated by pro- and anti-angiogenic factors. Anti-angiogenic agents target the interconnected network of angiogenic factors to inhibit neovascularization, which subsequently impedes tumor growth. Due to the complexity of this network, optimizing anti-angiogenic cancer treatments requires detailed knowledge at a systems level. In this study, we constructed a tumor tissue-based model to better understand how the angiogenic network is regulated by opposing mediators at the extracellular level. We consider the network comprised of two pro-angiogenic factors: vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), and two anti-angiogenic factors: thrombospondin-1 (TSP1) and platelet factor 4 (PF4). The model's prediction of angiogenic factors' distribution in tumor tissue reveals the localization of different factors and indicates the angiogenic state of the tumor. We explored how the distributions are affected by the secretion of the pro- and anti-angiogenic factors, illustrating how the angiogenic network is regulated in the extracellular space. Interestingly, we identified a counterintuitive result that the secretion of the anti-angiogenic factor PF4 can enhance pro-angiogenic ...Continue Reading
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Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced colorectal carcinoma
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