Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44(+) gastric cancer cells via attenuating Wnt signaling

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	Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44(+) gastric cancer cells via attenuating Wnt signaling
	Wang, Bin 1,2,3; Liu, Jia 4; Ma, Lei Na 5; Xiao, Hua Liang 6; Wang, Ya Zhou 7; Li, Yan1 ; Wang, Zhe 2,3; Fan, Linli 1; Lan, Chunhui 1; Yang, Min 1
刊名	JOURNAL OF GASTROENTEROLOGY
	2013-07-01
卷号	48 期号:7 页码:798-808
关键词	Gastric carcinoma Cancer stem cells Gene therapy Dickkopf-1
ISSN号	0944-1174
通讯作者	Chen, DF
中文摘要	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). 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.
英文摘要	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).
学科主题	Gastroenterology & Hepatology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Gastroenterology & Hepatology
研究领域[WOS]	Gastroenterology & Hepatology
关键词[WOS]	STEM-CELLS ; IN-VIVO ; HEPATOCELLULAR-CARCINOMA ; ONCOLYTIC ADENOVIRUS ; SMALL-INTESTINE ; GENE ; PROLIFERATION ; EXPRESSION ; IDENTIFICATION ; DESTRUCTION
收录类别	SCI
原文出处	10.1007/s00535-012-0711-z
语种	英语
WOS记录号	WOS:000321971500002
公开日期	2014-07-17
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/16542]
专题	海洋研究所_实验海洋生物学重点实验室
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.,...&Wang, Jun.(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.