title: A fusion protein with the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment: Simultaneous blocking of VEGF receptor-1 and 2.
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.
authors.affiliation: Department of Orthopedics, Hualien Armed Forces Hospital, Hualien, Taiwan, ROC.
authors.forename: Feng-Jen
authors.initials: FJ
authors.lastname: Tseng
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Nu-Man
authors.initials: NM
authors.lastname: Tsai
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Lee
authors.forename: Yo-Shong
authors.initials: YS
authors.lastname: Chung
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Yen-Ku
authors.initials: YK
authors.lastname: Liu
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Huang
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Hwang
authors.forename: Yiu-Kay
authors.initials: YK
authors.lastname: Lai
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Liao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2