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: | 1-十一月-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 |
顯示於類別: | 期刊論文 |