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

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.