Antitumor activity of a recombinant soluble ectodomain of mutant human fibroblast growth factor receptor-2 IIIc

• Published in: Molecular cancer therapeutics 2011-09, Vol.10 (9), p.1656-1666
• Main Authors: Wang, Ju, Liu, Xue-ting, Huang, Hui, Xiao, Gang, Zhou, Zhi-you, Chen, Yang, Yu, Zhi-hong, He, Shui-lian, Chen, An-an, Wang, Ding-ding, He, Ying, Zhang, Zhi-cheng, Hong, An
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation - drug effects; Female; Humans; Kaplan-Meier Estimate; Ligands; Mice; Mice, Inbred BALB C; Mice, Nude; Mutant Proteins - genetics; Mutant Proteins - pharmacology; Mutant Proteins - therapeutic use; Neoplasm Metastasis - drug therapy; Neoplasm Metastasis - pathology; Neoplasms - drug therapy; Neoplasms - mortality; Neoplasms - pathology; Neovascularization, Physiologic - drug effects; NIH 3T3 Cells; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptide Fragments - therapeutic use; Protein Binding; Receptor, Fibroblast Growth Factor, Type 2 - chemistry; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 2 - pharmacology; Receptor, Fibroblast Growth Factor, Type 2 - therapeutic use; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Signal Transduction - drug effects; Tumor Burden - drug effects; Xenograft Model Antitumor Assays
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-11-0163

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.