title: Construction of a disulfide-stabilized diabody against fibroblast growth factor-2 and the inhibition activity in targeting breast cancer.
abstract: Fibroblast growth factor-2 (FGF-2) is one of the most important angiogenic factors to promote tumor growth, progression and metastasis. Neutralizing antibodies against FGF-2 may suppress the growth of tumor cells by blocking the FGF-2 signaling pathway. In this study, a disulfide-stabilized diabody (ds-Diabody) that specifically targets FGF-2 was designed. Compared to its parent antibody, the introduction of disulphide bonds in the diabody could significantly increase the stability of ds-Diabody and maintain its antigen binding activity. The ds-Diabody against FGF-2 could effectively inhibit the tube formation and migration of vascular endothelial cells and block the proliferation and invasion of human breast cancer cells. In the mouse model of breast cancer xenograft tumors, the ds-Diabody against FGF-2 could significantly inhibit the growth of tumor cells. Moreover, the densities of microvessels stained with CD31 and lymphatic vessels stained with LYVE1 in tumors showed a significant decrease following treatment with the ds-Diabody against FGF-2. Our data indicated that the ds-Diabody against FGF-2 could inhibit tumor angiogenesis, lymphangiogenesis and tumor growth.
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Yaxiong
authors.identifier: http://orcid.org/0000-0003-1058-6546
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, the First Clinical School in Jinan University, Guangzhou, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Lao
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Haowu
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.
authors.forename: Yiye
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Shenzhen Key Laboratory of Birth Defects in Baoan Maternal and Child Health Care Affiliated Hospital in Jinan University, Shenzhen, China.
authors.forename: Likuan
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute in Jinan University, Guangzhou, China.|Shenzhen Key Laboratory of Birth Defects in Baoan Maternal and Child Health Care Affiliated Hospital in Jinan University, Shenzhen, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Deng
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology*; D042583:Lymphangiogenesis / Q000187:drug effects; D061986:MCF-7 Cells; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004220:Disulfides; D007136:Immunoglobulins; D016222:Fibroblast Growth Factor 2
keywords: Breast cancer; FGF-2; Pichia pastoris; ds-Diabody; tumor angiogenesis