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学科主题: 临床医学
题名:
Suppression of breast tumor growth by DNA vaccination against phosphatase of regenerating liver 3
作者: Lv, J.1; Liu, C.1; Huang, H.1; Meng, L.1; Jiang, B.1,2; Cao, Y.1,3; Zhou, Z.1; She, T.1; Qu, L.1; Song, S. Wei4; Shou, C.1
关键词: PRL-3 ; DNA vaccine ; mouse ; breast cancer
刊名: GENE THERAPY
发表日期: 2013-08-01
DOI: 10.1038/gt.2013.5
卷: 20, 期:8, 页:834-845
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: EPITHELIAL-MESENCHYMAL TRANSITION ; MOUSE MELANOMA-CELLS ; PRL PHOSPHATASES ; MONOCLONAL-ANTIBODIES ; ANTITUMOR IMMUNITY ; CANCER-IMMUNOTHERAPY ; IN-VITRO ; ANTIGEN ; METASTASIS ; VACCINES
英文摘要:

Phosphatase of regenerating liver (PRL)-3 is highly expressed in multiple cancers and has important roles in cancer development. Some small-molecule inhibitors and antibodies targeting PRL-3 have been recently reported to inhibit tumor growth effectively. To determine whether PRL-3-targeted DNA vaccination can induce immune response to prevent or inhibit the tumor growth, we established mouse D2F2 breast cancer cells expressing PRL-3 (D2F2/PRL-3) and control cells (D2F2/NC) with lentivirus, and constructed pVAX1-Igk-PRL-3 plasmid (named as K-P3) as DNA vaccine to immunize BALB/c mice. We found that the K-P3 vaccine delivered by gene gun significantly prevented the growth of D2F2/PRL-3 compared with pVAX1-vector (P<0.01), but not of D2F2/NC, and improved the survival of D2F2/PRL-3-innoculated mice. Both PRL-3-targeted cytotoxic T lymphocytes (CTLs) and T-helper type 1 cell immune response (production of high levels of interferon-gamma and tumor necrosis factor-alpha) were found to be involved in the preventive effect. Furthermore, PRL-3-targeted DNA immunization inhibited tumor growth of D2F2/PRL-3 cells in mice. We also evaluated the potential of immunization with PRL-3 protein, but no significant therapeutic or preventive effect was obtained on tumor growth. To enhance the immunity of PRL-3, we incorporated different molecular adjuvants, such as Mycobacterium tuberculosis heat-shock protein, CTL antigen 4 and M. tuberculosis T-cell stimulatory epitope (MT), into K-P3 vaccine for expressing the fusion proteins. We found that these adjuvant molecules did not significantly improve the antitumor activity of PRL-3 vaccine, but enhanced the production of PRL-3 antibodies in immunized mice. Summarily, our findings demonstrate that PRL-3-targeted DNA vaccine can generate significantly preventive and therapeutic effects on the growth of breast cancer expressing PRL-3 through the induction of cellular immune responses to PRL-3.

语种: 英语
所属项目编号: 2009CB521805 ; 81071732 ; 30973407
项目资助者: National 973 Program of China ; National Nature Science Foundation of China
WOS记录号: WOS:000322906300006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65337
Appears in Collections:北京大学临床肿瘤学院_胃肠肿瘤中心_期刊论文

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作者单位: 1.Changzhi Med Coll, Dept Biochem, Changzhi, Shanxi, Peoples R China
2.Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100142, Peoples R China
3.Peking Univ, Canc Hosp & Inst, Dept Minimally Invas Gastrointestinal Surg, Beijing 100142, Peoples R China
4.Peking Univ, Canc Hosp & Inst, Clin Res Lab, Beijing 100142, Peoples R China

Recommended Citation:
Lv, J.,Liu, C.,Huang, H.,et al. Suppression of breast tumor growth by DNA vaccination against phosphatase of regenerating liver 3[J]. GENE THERAPY,2013,20(8):834-845.
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