Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer

2008 ◽  
Vol 43 (3) ◽  
pp. 216-224 ◽  
Author(s):  
Seiji Futagami ◽  
Atsushi Tatsuguchi ◽  
Tetsuro Hiratsuka ◽  
Tomotaka Shindo ◽  
Akane Horie ◽  
...  
Blood ◽  
2005 ◽  
Vol 105 (4) ◽  
pp. 1405-1407 ◽  
Author(s):  
Kyung Hee Hong ◽  
Jewon Ryu ◽  
Ki Hoon Han

Abstract Monocyte chemoattractant protein-1 (MCP-1) has been recognized as an angiogenic chemokine. In the present study, we investigated the detailed mechanism by which MCP-1 induces angiogenesis. We found that MCP-1 up-regulated hypoxia-inducible factor 1α (HIF-1α) gene expression in human aortic endothelial cells (HAECs), which induced vascular endothelial growth factor-A165 (VEGF-A165) expression in the aortic wall and HAECs through activation of p42/44 mitogen-activated protein kinase (MAPK). In vivo angiogenesis assay using chick chorioallantoic membrane (CAM) showed that MCP-1–induced angiogenesis was as potent as that induced by VEGF-A165 and completely inhibited by a VEGF inhibitor, Flt2-11. The inhibition of RhoA small G protein did not affect MCP-1–induced VEGF-A165 production and secretion but completely blocked both MCP-1– and VEGF-A–induced new vessel formation, as determined by CAM assay. These results suggest that MCP-1–induced angiogenesis is composed largely of 2 sequential steps: the induction of VEGF-A gene expression by MCP-1 and the subsequent VEGF-A–induced angiogenesis.


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