標題: A fusion protein with the receptor binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment
作者: Tseng, Feng-Jen
Chen, Yu-Cheng
Lin, Yu-Ling
Tsai, Nu-Man
Lee, Ru-Ping
Chung, Yo-Shong
Chen, Chia-Hung
Liu, Yen-Ku
Huang, Yu-Shan
Hwang, Chia-Hsiang
Lai, Yiu-Kay
Liao, Kuang-Wen
生物科技學系
分子醫學與生物工程研究所
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
關鍵字: VEGF;vascular endothelial growth factor;RBDV;receptor-binding domain of VEGF;ADCC;antibody dependent cellular cytotoxicity;angiogenesis;Ig;immunoglobulin
公開日期: 1-Nov-2010
摘要: 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.
URI: http://dx.doi.org/10.4161/cbt.10.9.13230
http://hdl.handle.net/11536/31978
ISSN: 1538-4047
DOI: 10.4161/cbt.10.9.13230
期刊: CANCER BIOLOGY & THERAPY
Volume: 10
Issue: 9
起始頁: 869
結束頁: 877
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