A novel single-chain variable fragment antibody against FGF-1 inhibits the growth of breast carcinoma cells by blocking the intracrine pathway of FGF-1.

The fibroblast growth factors (FGFs) are important for embryo development, wound healing, hematopoiesis, and angiogenesis. FGF-1, a member of FGF family, is involved in both receptor-dependent pathways and an intracrine pathway. Studies have recently shown that FGF-1 is overexpressed in the early stages of several kinds of cancer. Thus, FGF-1 is a candidate for cancer immunotargeting. To study the potential use of therapeutic antibodies against FGF-1, a monoclonal hybridoma 1C9 secreting monoclonal antibody specific for FGF-1 was developed. Then, a single-chain variable fragment (scFv) antibody was genetically engineered from hybridama 1C9. The binding of the scFv1C9 to the antigen FGF-1 was demonstrated by ELISA and immunoprecipitation assays. Functional analysis showed that the overexpressed scFv1C9 in MCF-7 cells targeted endogenous FGF-1 and prevented the translocation of FGF-1 into the nucleus, resulting in the blockade of the intracrine pathway of FGF-1, which caused the G1 arrest by p21 up-regulation. These results suggest that the generated scFv1C9 is an effective inhibitor of the intracrine pathway of FGF-1 and has a potential application as anti-tumoral agent in breast cancer.