Studies on breast cancer treatment mediated by scFv1C9 specific for FGF-1

来源 :第四届细胞结构与功能的信号基础研讨会 | 被引量 : 0次 | 上传用户:woxxlong
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  The fibroblast growth factors (FGFs) are important for embryo development, wound healing, hematopoiesis, and angiogenesis.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 single-chain variable fragment (scFv) antibody was genetically engineered from hybridama 1 C9.Coexpression of GFP-scFv1C9 and HA-FGF-1 in MCF-7 cells, there were found that they presented interaction in immunoprecipitational complex.The results showed that the recombinant scFv1C9 retained enough affinity to bind with the antigen in vitro.To analyze the neutralizing function of scFv1C9, the scFv1C9 gene was stably transfected in MCF-7 cell mediated by lentivirus, the cells were subcutaneously injected into the right flanks of SCID nude mice to observe the tumorigenesis.The results showed cells neutralizied FGF-1 in advance apparently reduced tumor formation, which further verified that FGF-1 involved in the occurrence of breast cancer.It has been reported that FGF-1 is involved in both receptor-dependent pathways and an intracrine pathway.Additional 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 finally caused the G1 arrest by p21 up-regulation.Further study in vivo also showed that scFv1C9 significantly inhibited the growth of breast cancer xenograft mediated by electroporatio.The tumors were cut into slides and subjected for immunohistochemistry staining of Ki-67 and CD31, it showed that the Ki-67 index and MVD of the scFv1C9 group was reduced comparing with control group.These results suggest that the generated scFv1C9 is an effective inhibitor of the intracrine pathway of FGF-1 and has a potential application in breast cancer therapy.
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