Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent anti-angiogenic effects. Issue 2 (28th July 2016)

• Record Type: Journal Article
• Authors: Li, Dong; Xie, Kun; Zhang, Longzhen; Yao, Xuejing; Li, Hongwen; Xu, Qiaoyu; Wang, Xin; Jiang, Jing; Fang, Jianmin
• Is Part Of: Cancer letters. Volume 377:Issue 2(2016)
• Page Start: 164
• Page End: 173
• Publication Date: 2016-07-28
• Subjects: VEGF -- FGF-2 -- Dual decoy receptor -- Angiogenesis -- Anti-angiogenic therapy -- Cancer therapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.04.036
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: VEGF and FGF-2 play critical roles in tumor and ocular neovascularization. Dual blockade of VEGF and FGF may result in an additive anti-angiogenesis effect. A decoy receptor fusion protein, VF-Trap, can bind simultaneously to both VEGF and FGF-2. VF-Trap has potent anti-angiogenesis efficacy both in vitro and in vivo . VF-Trap holds potential to be developed as a therapeutic reagent. Abstract: Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF or FGF-2) are potent pro-angiogenic factors and play a critical role in cancer development and progression. Clinical anti-VEGF therapy trials had a major challenge due to upregulated expression of other pro-angiogenic factor, like FGF-2. This study developed a novel chimeric decoy receptor VF-Trap fusion protein to simultaneously block activity of both VEGF and FGF pathways in order to achieve an additive or synergistic anti-tumor effect. Our in vitro data showed that VF-Trap potently blocked proliferation and migration of both VEGF- and FGF-2-induced vascular endothelial cells. In animal models, treatment of xenograft tumors with VF-Trap resulted in significant inhibition of tumor growth compared to blockage of the single molecule, like VEGF or FGF blocker. In addition, VF-Trap was also more potent in inhibition of ocular angiogenesis in a mouse oxygen-induced retinopathy (OIR) model. These data demonstrated the potent anti-angiogenic effects of this novel VF-Trap fusion protein on blockage of VEGF and FGF-2 activity in vitro and in animal models. Further study will assess its effects in clinic as a therapeutic agent for angiogenesis-related disorders, such as cancer and ocular vascular diseases.