Abstract
Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Angiogenesis Inhibitors / metabolism
-
Angiogenesis Inhibitors / pharmacology
-
Angiogenesis Inhibitors / therapeutic use*
-
Animals
-
Antibody-Dependent Cell Cytotoxicity
-
Cell Line, Tumor
-
Cell Movement
-
Cell Proliferation / drug effects
-
Humans
-
Immunoglobulin Fc Fragments
-
Melanoma, Experimental / drug therapy*
-
Melanoma, Experimental / metabolism
-
Melanoma, Experimental / pathology
-
Mice
-
Mice, Inbred C57BL
-
Protein Binding
-
Recombinant Fusion Proteins / metabolism
-
Recombinant Fusion Proteins / pharmacology
-
Recombinant Fusion Proteins / therapeutic use
-
Signal Transduction / drug effects
-
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
-
Vascular Endothelial Growth Factor A / chemistry
-
Vascular Endothelial Growth Factor A / metabolism
-
Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
-
Vascular Endothelial Growth Factor Receptor-1 / metabolism
-
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
-
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
-
Angiogenesis Inhibitors
-
Immunoglobulin Fc Fragments
-
Recombinant Fusion Proteins
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factor Receptor-1
-
Vascular Endothelial Growth Factor Receptor-2