A fusion fragment from Flt-1 and KDR, acted as VEGF decoy receptor and exhibited anti-tumor function.
Angiogenesis is important in tumor development. Vascular endothelial growth factor (VEGF) is involved in this process. In this report, we constructed a recombinant protein (called FK) by fusing the second immunoglobulin-like (Ig-like) domain of a human fms-like tyrosine kinase (Flt-1) with the third Ig-like domain of human kinase insert domain-containing receptor (KDR). FK bound to VEGF(165) in a dose-dependent manner with a disocciation constant (Kd) of 2.7 pM. In addition, FK specifically inhibited the proliferation of human microvascular endothelial cell (HMEC) and human umbilical vein endothelial Cell (HUVEC) stimulated by VEGF(165). Subsequent studies also demonstrate that FK efficaciously suppresses growth of a variety of tumors, which could make FK a potential drug candidate in anti-tumor therapy.
Li
Zhuang-Lin
ZL
State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
Yao
Xue-Jing
XJ
Liu
Wei-Feng
WF
Chen
Guan-Jun
GJ
D000970:Antineoplastic Agents / Q000378:metabolism*; D001688:Biological Products / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D001688:Biological Products; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2