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学科主题: 基础医学
题名:
Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21
作者: Shih, Yu-Tsung1; Wang, Mei-Cun1; Zhou, Jing2,3,4; Peng, Hsin-Hsin5; Lee, Ding-Yu1; Chiu, Jeng-Jiann1,6
刊名: GUT
发表日期: 2015-07-01
DOI: 10.1136/gutjnl-2013-306302
卷: 64, 期:7, 页:1132-1147
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: HEPATOCELLULAR-CARCINOMA ; STEM-CELLS ; CANCER ; TUMORS ; INFLAMMATION ; FIBROBLASTS ; RECRUITMENT ; SUPPRESSOR ; EXPRESSION ; SURVIVAL
英文摘要:

Objectives Endothelial progenitor cells (EPCs) circulate with increased numbers in the peripheral blood of patients with highly-vascularised hepatocellular carcinoma (HCC) and contribute to angiogenesis and neovascularisation. We hypothesised that angiogenic EPCs, that is, colony forming unit-endothelial cells (CFU-ECs), and outgrowth EPCs, that is, endothelial colony-forming cells, may exert paracrine effects on the behaviours and metastatic capacities of human hepatoma cells.

Design Various molecular and functional approaches ranging from in vitro cell culture studies on molecular signalling to in vivo investigations on cell invasion and orthotropic transplantation models in mice and clinical specimens from patients with HCC were used.

Results Monocyte chemotactic protein-1 (MCP-1) was identified as a critical mediator released from CFU-ECs to contribute to the chemotaxis of Huh7 and Hep3B cells by inducing their microRNA-21 (miR-21) biogenesis through the C-C chemokine receptor-2/c-Jun N-terminal kinase/activator protein-1 signalling cascade. CFU-EC-induction of miR-21 in these cells activated their Rac1 and matrix metallopeptidase-9 by silencing Rho GTPase-activating protein-24 and tissue inhibitor of metalloproteinase-3, respectively, leading to increased cell mobility. MCP-1-induction of miR-21 induced epithelial-mesenchymal transformation of Huh7 cells in vitro and their intrahepatic metastatic capability in vivo. Moreover, increased numbers of MCP-1(+) EPCs and their positive correlations with miR-21 induction and metastatic stages in human HCC were found.

Conclusions Our results provide new insights into the complexity of EPC-HCC interactions and indicate that anticancer therapies targeting either the MCP-1 released from angiogenic EPCs or the miR-21 biogenesis in HCC cells may prevent the malignant progression of primary tumours.

语种: 英语
所属项目编号: 101-2321-B-400-001
项目资助者: Taiwan NSC
WOS记录号: WOS:000356022700018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57470
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Natl Hlth Res Inst, Inst Cellular & Syst Med, Miaoli 350, Taiwan
2.Peking Univ, Dept Physiol & Pathophysiol, Basic Med Coll, Beijing 100871, Peoples R China
3.Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
4.Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA
5.Chang Gung Univ, Ctr Mol & Clin Immunol, Taoyuan, Taiwan
6.Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu, Taiwan

Recommended Citation:
Shih, Yu-Tsung,Wang, Mei-Cun,Zhou, Jing,et al. Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21[J]. GUT,2015,64(7):1132-1147.
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