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2015 ; 2015
(ä): 908757
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Activation of Apoptotic Signal in Endothelial Cells through Intracellular
Signaling Molecules Blockade in Tumor-Induced Angiogenesis
#MMPMID26346668
Bazmara H
; Soltani M
; Raahemifar K
; Sefidgar M
; Bazargan M
; Naeenian MM
; Elkamel A
Biomed Res Int
2015[]; 2015
(ä): 908757
PMID26346668
show ga
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.