title: MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer.
abstract: The gene MTDH/AEG-1 is overexpressed in more than 40% of breast cancer patients, and it is associated with poor clinical outcomes. Previous studies have indicated that MTDH/AEG-1 could promote metastatic lung-seeding and enhance chemoresistance. Therefore, MTDH/AEG-1 could be a candidate target against breast cancer lung metastasis. We demonstrated that MTDH/AEG-1-based DNA vaccine, delivered by attenuated Salmonella typhimurium, could evoke strong CD8(+) cytotoxic-T-cell mediated immune responses against breast cancer. This vaccine showed anti-tumor growth and metastasis efficacy in a prophylactic setting. Importantly, in a therapeutic model, MTDH/AEG-1 vaccine was proved to increase chemosensitivity to doxorubicin and inhibit breast cancer lung metastasis. This vaccine could also prolong the life span of tumor-bearing mice without significant side effects in vivo. These results suggested that this novel DNA vaccine was effective in the inhibition of breast cancer growth and metastasis, and this vaccine in combination with chemotherapies offered new strategies for the clinical therapeutics of breast cancer metastasis.
authors.affiliation: Institute of Ningde Urological Research and Department of Urology, Affiliated Mindong Hospital of Fujian Medical University, No. 89, Fu'an, Fujian, 355000, China.
authors.forename: Ben-Jiang
authors.initials: BJ
authors.lastname: Qian
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Liu
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lin
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Liu
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Luo
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Hui-Zhang
authors.initials: HZ
authors.lastname: Li
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D004317:Doxorubicin