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BioMed Research International
Volume 2015 (2015), Article ID 908757, 12 pages
http://dx.doi.org/10.1155/2015/908757
Research Article

Activation of Apoptotic Signal in Endothelial Cells through Intracellular Signaling Molecules Blockade in Tumor-Induced Angiogenesis

1Department of Mechanical Engineering, K.N.T. University of Technology, Tehran, Iran
2Division of Nuclear Medicine, Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
3Electrical & Computer Department, Ryerson University, Toronto, ON, Canada
4Department of Engineering and Technology, IKI University, Qazvin, Iran
5Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada

Received 5 February 2015; Revised 7 June 2015; Accepted 11 June 2015

Academic Editor: Tatsuya Akutsu

Copyright © 2015 Hossein Bazmara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor-induced angiogenesis is the bridge between avascular and vascular tumor growth phases. In tumor-induced angiogenesis, endothelial cells start to migrate and proliferate toward the tumor and build new capillaries toward the tumor. There are two stages for sprout extension during angiogenesis. The first stage is prior to anastomosis, when single sprouts extend. The second stage is after anastomosis when closed flow pathways or loops are formed and blood flows in the closed loops. Prior to anastomosis, biochemical and biomechanical signals from extracellular matrix regulate endothelial cell phenotype; however, after anastomosis, blood flow is the main regulator of endothelial cell phenotype. In this study, the critical signaling pathways of each stage are introduced. A Boolean network model is used to map environmental and flow induced signals to endothelial cell phenotype (proliferation, migration, apoptosis, and lumen formation). Using the Boolean network model, blockade of intracellular signaling molecules of endothelial cell is investigated prior to and after anastomosis and the cell fate is obtained in each case. Activation of apoptotic signal in endothelial cell can prevent the extension of new vessels and may inhibit angiogenesis. It is shown that blockade of a few signaling molecules in endothelial cell activates apoptotic signal that are proposed as antiangiogenic strategies.