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| Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44(+) gastric cancer cells via attenuating Wnt signaling | |
Wang, Bin1,2,3 ; Liu, Jia4; Ma, Lei Na5; Xiao, Hua Liang6; Wang, Ya Zhou7; Li, Yan1; Wang, Zhe2,3; Fan, Linli1; Lan, Chunhui1; Yang, Min1; Hu, Lu1; Wei, Yanlin1; Bian, Xiu Wu2,3; Chen, Dongfeng1; Wang, Jun1; Chen, DF
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| 2013-07-01 | |
| 发表期刊 | JOURNAL OF GASTROENTEROLOGY
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| ISSN | 0944-1174 |
| 卷号 | 48期号:7页码:798-808 |
| 文章类型 | Article |
| 摘要 | Gastric cancer stem cells (CSCs), which require activation of Wnt signaling to maintain their self-renewal and tumorigenicity, are proposed to be critical targets for effective therapy of gastric carcinomas. Gene therapies that are delivered by adenovirus of serotype 5 (Ad5) or chimeric 5/35(Ad5/35) adenovirus have shown promise for treating various cancers. Here we aimed to develop a gene therapy strategy that targeted gastric CSCs (CD44(+) cells).; Gastric cancer stem cells (CSCs), which require activation of Wnt signaling to maintain their self-renewal and tumorigenicity, are proposed to be critical targets for effective therapy of gastric carcinomas. Gene therapies that are delivered by adenovirus of serotype 5 (Ad5) or chimeric 5/35(Ad5/35) adenovirus have shown promise for treating various cancers. Here we aimed to develop a gene therapy strategy that targeted gastric CSCs (CD44(+) cells). CD44(+) cells were isolated by fluorescence activated cell sorting from both primary gastric cancer cells and cell lines. Expression of adenovirus receptors was examined in CD44(+) and CD44(-) cells. A potent Wnt antagonist Dickkopf-1 (DKK1) was delivered into CD44(+) cells using Ad5/35 (Ad5/35-DKK1). The therapeutic outcomes were evaluated. Expression of Coxsakievirus adenovirus receptor for Ad5 was significantly reduced, while abundance of CD46, the receptor for Ad5/35, was slightly higher in CD44(+) cells. Accordingly, CD44(+) cells were sensitive to Ad5/35 infection, but not to Ad5. Ad5/35-DKK1 introduced DKK1 into CD44(+) cells and deactivated endogenous Wnt/beta-catenin signaling efficiently. Overexpression of DKK1 inhibited survival, anchorage-independent colony formation, and invasion of CD44(+) cells, which were restored by a GSK-3 specific inhibitor BIO-acetoxime. More importantly, introduction of DKK1 abrogated the tumorigenicity of CD44(+) cells in vivo. However, Ad5/35-DKK1 only showed minimal cytotoxicity to normal tissue-derived cells, L-02 and GES-1. We developed, for the first time, a novel Ad5/35-DKK1-based approach to abrogate Wnt signaling in CSCs and demonstrated that gastric CSC-targeting gene therapy was effective in preclinical experiments. |
| 关键词 | Gastric Carcinoma Cancer Stem Cells Gene Therapy Dickkopf-1 |
| 学科领域 | Gastroenterology & Hepatology |
| DOI | 10.1007/s00535-012-0711-z |
| URL | 查看原文 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Gastroenterology & Hepatology |
| WOS类目 | Gastroenterology & Hepatology |
| WOS记录号 | WOS:000321971500002 |
| WOS关键词 | STEM-CELLS ; IN-VIVO ; HEPATOCELLULAR-CARCINOMA ; ONCOLYTIC ADENOVIRUS ; SMALL-INTESTINE ; GENE ; PROLIFERATION ; EXPRESSION ; IDENTIFICATION ; DESTRUCTION |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/16542 |
| 专题 | 实验海洋生物学重点实验室 |
| 通讯作者 | Chen, DF |
| 作者单位 | 1.Third Mil Med Univ, Dept Gastroenterol, Inst Surg Res, Daping Hosp, Chongqing 400042, Peoples R China 2.Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China 3.Third Mil Med Univ, Southwest Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China 4.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China 5.Ocean Univ China, Sch Med & Pharm, Dept Mol Biol, Qingdao 266003, Peoples R China 6.Third Mil Med Univ, Dept Pathol, Inst Surg Res, Daping Hosp, Chongqing 400042, Peoples R China 7.Chongqing Univ, Bioengn Coll, Minist Educ, Key Lab Biorheol Sci & Technol, Chongqing 400030, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Bin,Liu, Jia,Ma, Lei Na,et al. Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44(+) gastric cancer cells via attenuating Wnt signaling[J]. JOURNAL OF GASTROENTEROLOGY,2013,48(7):798-808. |
| APA | Wang, Bin.,Liu, Jia.,Ma, Lei Na.,Xiao, Hua Liang.,Wang, Ya Zhou.,...&Chen, DF.(2013).Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44(+) gastric cancer cells via attenuating Wnt signaling.JOURNAL OF GASTROENTEROLOGY,48(7),798-808. |
| MLA | Wang, Bin,et al."Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44(+) gastric cancer cells via attenuating Wnt signaling".JOURNAL OF GASTROENTEROLOGY 48.7(2013):798-808. |
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| Chimeric 535 adenovi（686KB） | 限制开放 | CC BY-NC-SA | 浏览 | |||
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