title: Antitumor activity of a recombinant soluble ectodomain of mutant human fibroblast growth factor receptor-2 IIIc.
abstract: The fibroblast growth factor (FGF) signaling pathway is a recognized target of cancer therapy. We have developed a strong inhibitor (S252W mutant soluble ectodomain of FGF recptor-2 IIIc, msFGFR2) that binds FGFs and blocks the activation of FGFRs. Thermodynamic binding studies indicated that msFGFR2 bound FGF-2 16.9 times as strongly as wild-type soluble FGFR2IIIc ectodomain (wsFGFR2). It successfully suppressed the growth, angiogenesis, and metastasis of two tumor cell lines in vitro and in vivo, and it potently inhibited cancer cell proliferation but not normal cell proliferation. Therefore, msFGFR2 is a useful probe for FGF-dependent signaling pathways and a potential broad-spectrum antitumor agent.
authors.affiliation: Guangdong Provincial Key Laboratory of Bio-engineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China. wang_ju1688@yahoo.cn
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.forename: Xue-ting
authors.initials: XT
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Gang
authors.initials: G
authors.lastname: Xiao
authors.forename: Zhi-you
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Yu
authors.forename: Shui-lian
authors.initials: SL
authors.lastname: He
authors.forename: An-an
authors.initials: AA
authors.lastname: Chen
authors.forename: Ding-ding
authors.initials: DD
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Zhi-cheng
authors.initials: ZC
authors.lastname: Zhang
authors.forename: An
authors.initials: A
authors.lastname: Hong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050505:Mutant Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D050505:Mutant Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C569420:msFGFR2 protein; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2