title: A novel decoy receptor fusion protein for FGF-2 potently inhibits tumour growth.
abstract: BACKGROUND
  Antiangiogenic therapies have been proven effective in cancer treatment. Fibroblast growth factor-2 (FGF-2) has been functionally implicated in tumour angiogenesis and is an important target of antiangiogenic therapies. The aim of this work was to develop a novel FGF-2 inhibitor for cancer therapy.
  
  
  METHODS
  Eleven fusion proteins were developed by fusing various truncated extracellular regions of FGFR1 with the Fc region of IgG1. The optimal decoy receptor fusion protein with the highest binding affinity for FGF-2 was identified by an FGF-2-binding assay and its potential antitumour effects were investigated.
  
  
  RESULTS
  We obtained a soluble decoy receptor fusion protein with the highest binding activity for FGF-2, named FGF-Trap. Fibroblast growth factor-Trap significantly abolished FGF-2-stimulated activation of FGF signalling as demonstrated by its suppression of FGF-2-mediated phosphorylation of Erk1/2 and Akt, upregulation of cyclins D1 and E and the increase in mRNA levels of vascular endothelial growth factor R1 and R2 (VEGFR1 and VEGFR2). Furthermore, FGF-Trap effectively suppressed FGF-2-induced proliferation and migration of human umbilical vein endothelial cells (HUVECs) in vitro. Most importantly, FGF-Trap potently inhibited tumour growth and angiogenesis in Caki-1 and A549 xenograft models in vivo.
  
  
  CONCLUSIONS
  Fibroblast growth factor-Trap potently inhibits tumour growth by blocking FGF-2 signalling pathways and could be an effective therapeutic agent for cancer patients.
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: K
authors.initials: K
authors.lastname: Xie
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: J
authors.initials: J
authors.lastname: Fang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D048708:Cell Growth Processes / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1