title: 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.
abstract: 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.
authors.affiliation: Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun, China.
authors.forename: Heng-Liang
authors.initials: HL
authors.lastname: Shi
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Khalissa
authors.initials: K
authors.lastname: Deffar
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Dong
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Liu
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Fu
authors.forename: Da-Xue
authors.initials: DX
authors.lastname: Zheng
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Xing-Zhi
authors.initials: XZ
authors.lastname: Wang
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006825:Hybridomas / Q000737:chemistry / Q000378:metabolism; D056747:Immunomodulation; D051379:Mice; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D057127:Single-Chain Antibodies / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; D016220:Fibroblast Growth Factor 1