IR@PKUHSC  > 北京大学基础医学院
学科主题基础医学
Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21
Shih, Yu-Tsung1; Wang, Mei-Cun1; Zhou, Jing2,3,4; Peng, Hsin-Hsin5; Lee, Ding-Yu1; Chiu, Jeng-Jiann1,6
刊名GUT
2015-07-01
DOI10.1136/gutjnl-2013-306302
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
WOS记录号WOS:000356022700018
通讯作者邮箱jjchiu@nhri.org.tw
项目编号101-2321-B-400-001
资助机构Taiwan NSC
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57470
专题北京大学基础医学院
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
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GB/T 7714
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.
APA Shih, Yu-Tsung,Wang, Mei-Cun,Zhou, Jing,Peng, Hsin-Hsin,Lee, Ding-Yu,&Chiu, Jeng-Jiann.(2015).Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21.GUT,64(7),1132-1147.
MLA Shih, Yu-Tsung,et al."Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21".GUT 64.7(2015):1132-1147.
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