Adenovirus-mediated gene transfer of a truncated form of fibroblast growthfactor receptor inhibits growth of glioma cells both in vitro and in vivo

Basic fibroblast growth factor (FGF-2) and high affinity FGF receptor (FGFR ) have been detected in the nucleus as well as the cytoplasm of many human gliomas, and are known to stimulate cellular proliferation and angiogenesis in the tumors. To investigate the effects of inactivation of FGFR on the g rowth of malignant gliomas, we constructed a replication-deficient recombin ant adenovirus vector encoding a truncated form of chicken FGFR1 (AxCA Delt a FR). AxCA Delta FR-infected cells were confirmed to express truncated FGF R protein by immunoblotting and FGF-2-dependent clonogenicity of NIH3T3 cel ls was suppressed by infection with this virus vector. Then human malignant glioma cell lines U-251MG and T98G, both of which have been reported to ex press FGF-2 and FGFR, were infected with AxCA Delta FR. These infected cell s showed nuclear as well as cytoplasmic expression of a truncated FGFR prot ein. Proliferation rate and the ability to form colonies in soft agar of th e cells infected with this virus vector were significantly suppressed compa red with those of uninfected and lacZ-expressing adenovirus-infected cells. Moreover, intratumoral injection of AxCA Delta FR significantly suppressed the subcutaneous tumor growth of the glioma cells in nude mice. We conclud ed that inactivation of the cytoplasmic and nuclear FGFR using this truncat ed FGFR-expressing adenovirus vector can inhibit the growth of malignant gl iomas both in vitro and in vivo.