title: The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis.
abstract: Immunotherapy mediated by recombinant antibodies is an effective therapeutic strategy for a variety of cancers. In a previous study, we demonstrated that the fibroblast growth factor 1 (FGF-1)-specific recombinant antibody scFv1C9 arrests the cell cycle at the G0/G1 transition by blocking the intracrine FGF-1 pathway in breast cancer cells. Here, we further show that the overexpression of scFv1C9 in MCF-7 and MDA-MB-231 breast cancer cells by lentiviral infection resulted in decreased tumourigenicity, tumour growth and lung metastasis through FGF-1 neutralization. We found that scFv1C9 resulted in the up-regulation of p21, which in turn inhibited the expression of CDK2 and blocked cell cycle progression. To explore the potential role of scFv1C9 in vivo, we delivered the gene into solid tumours by electroporation, which resulted in significant inhibition of tumour growth. In tumour tissue sections, immunohistochemical staining of the cellular proliferation marker Ki-67 and the microvessel marker CD31 showed a reduction in the proliferative index and microvessel density, respectively, upon expression of scFv1C9 compared with the appropriate controls. Thus, our data indicate a central role for scFv1C9 in blocking the intracrine pathway of FGF-1, therefore, scFv1C9 could be developed in an effective therapeutic for breast cancer.
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun, China; Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.forename: Chunling
authors.initials: C
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Shuang
authors.initials: S
authors.lastname: Du
authors.forename: Rangjuan
authors.initials: R
authors.lastname: Cao
authors.forename: Jingying
authors.initials: J
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000235:genetics; D057127:Single-Chain Antibodies / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D057127:Single-Chain Antibodies; D016220:Fibroblast Growth Factor 1
keywords: FGF-1; lung metastasis; scFv1C9; tumour growth; tumourigenesis