Activation of Apoptotic Signal in Endothelial Cells through Intracellular Signaling Molecules Blockade in Tumor-Induced Angiogenesis.
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.
Department of Mechanical Engineering, K.N.T. University of Technology, Tehran, Iran.
Hossein
H
Bazmara
Department of Mechanical Engineering, K.N.T. University of Technology, Tehran, Iran ; Division of Nuclear Medicine, Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
M
M
Soltani
Electrical & Computer Department, Ryerson University, Toronto, ON, Canada.
Kaamran
K
Raahemifar
Department of Engineering and Technology, IKI University, Qazvin, Iran.
Mostafa
M
Sefidgar
Department of Mechanical Engineering, K.N.T. University of Technology, Tehran, Iran.
Majid
M
Bazargan
Department of Mechanical Engineering, K.N.T. University of Technology, Tehran, Iran.
Mojtaba Mousavi
MM
Naeenian
Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada.
Ali
A
Elkamel
D000818:Animals; D017209:Apoptosis; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction