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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/28489

    標題: A Novel Cancer Therapeutic Using Thrombospondin 1 in Dendritic Cells
    作者: Weng, Tzu-Yang
    Huang, Shih-Shien
    Yen, Meng-Chi
    Lin, Chi-Chen
    Chen, Yi-Ling
    Lin, Chiu-Mei
    Chen, Wei-Ching
    Wang, Chih-Yang
    Chang, Jang-Yang
    Lai, Ming-Derg
    貢獻者: 老人服務事業管理系
    日期: 2014-02
    上傳時間: 2015-05-06 21:18:08 (UTC+8)
    出版者: Nature Publishing Group
    摘要: Induction of thrombospondin 1 (TSP-1) is generally assumed to suppress tumor growth through inhibiting angiogenesis; however, it is less clear how TSP-1 in dendritic cells (DCs) influences tumor progression. We investigated tumor growth and immune mechanism by downregulation of TSP-1 in dendritic cells. Administration of TSP-1 small hairpin RNA (shRNA) through the skin produced anticancer therapeutic effects. Tumorinfiltrating CD4(+) and CD8(+) T cells were increased after the administration of TSP-1 shRNA. The expression of interleukin-12 and interferon-7 in the lymph nodes was enhanced by injection of TSP-1 shRNA. Lymphocytes from the mice injected with TSP-1 shRNA selectively killed the tumor cells, and the cytotoxicity of lymphocytes was abolished by depletion of CD8(+) T cells. Injection of CD11c(+) TSP-1 knockout (TSP-1-KO) bone marrow derived DCs (BMDCs) delayed tumor growth in tumorbearing mice. Similarly, antitumor activity induced by TSP-1-K0 BMDCs was abrogated by depletion of CD8(+) T cells. In contrast, the administration of shRNAs targeting TSP-2, another TSP family member, did not extend the survival of tumor-bearing mice. Finally, TSP-1 shRNA functioned as an innmunotherapeutic adjuvant to augment the therapeutic efficacy of Neu DNA vaccination. Collectively, the downregulation of TSP-1 in DCs produces an effective antitumor response that is opposite to the protumor effects by silencing of TSP-1 within tumor cells.
    關聯: Molecular therapy, v.22 n.2, pp.292-302
    Appears in Collections:[老人服務事業管理系] 期刊論文

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