Analysis of chemokine/chemokine system involoved in the growth of human hepatocellular carcinoma

人肝细胞癌生长中涉及的趋化因子/趋化因子系统分析

• 批准号: 15590674
• 负责人: ITOH Yoshito
• 金额: $ 2.05万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590674/
• 关键词: HCC; Chemokine; Chemokine Receptor; growth; MAPK; 転移

High level of CCR6 mRNA expression was quantified in human HCC cell lines, HuH7, PLC/PRF/5, and HepG2 cells as examined by TaqMan PCR. In flow cytometric analysis, also, CCR6 expression was enhanced on the surface of three HCC cell lines, HuH7, PLC/PRF/5, and HepG2 cells, similar to the results of mRNA expression by TaqMan PCR. The mRNA expression of CCL20, the ligand (chemokine) for CCR6, was demonstrated in HuH7, PLC/PRF/5, and HepG2 cells, all are identical to the cell lines expressing CCR6. CCL20 was secreted into the culture supernatant of HuH7, PLC/PRF/5, and HepG2 cells, but it was undetectable in the culture supernatant of other cell lines. MTT assay revealed that addition of CCL20 to the culture medium of HuH7 cells significantly (by approximately 170%, p<0.01) stimulated the proliferation of these cells expressing CCR6. Western blotting analysis clarified that the downstream signal transduction pathway of CCL20/CCR6 in HuH7 cells was mediated by p44/42 MAP kinase, but not by p38 MAP kinase or SPAK/JNK. Chemokines CCL20 did not show significant chemotactic activity towards hepatoma cell lines expressing high levels of their receptors, CCR6 on their surface. The present study indicates that some of the human hepatoma cells stimulate their own growth via the autocrine or paracrine mechanism mediated by chemokine-chemokine receptor system.

通过TaqMan PCR检测，在人HCC细胞系HuH 7、PLC/PRF/5和HepG 2细胞中定量CCR 6 mRNA的高水平表达。在流式细胞术分析中，也，CCR 6的表达增强的三个HCC细胞系，HuH 7，PLC/PRF/5，和HepG 2细胞的表面上，类似于通过TaqMan PCR的mRNA表达的结果。在HuH 7、PLC/PRF/5和HepG 2细胞中证实了CCL 20（CCR 6的配体（趋化因子））的mRNA表达，所有这些细胞都与表达CCR 6的细胞系相同。CCL 20分泌到HuH 7、PLC/PRF/5和HepG 2细胞的培养上清中，但在其它细胞系的培养上清中检测不到。MTT分析显示，向HuH 7细胞的培养基中添加CCL 20显著地（约170%，p<0.01）刺激了这些表达CCR 6的细胞的增殖。Western blotting分析表明，CCL 20/CCR 6在HuH 7细胞中的下游信号转导通路是由p44/42 MAP激酶介导的，而不是由p38 MAP激酶或SPAK/JNK介导的。趋化因子CCL 20对在其表面上表达高水平其受体CCR 6的肝癌细胞系没有显示出显著的趋化活性。本研究表明，某些人肝癌细胞通过趋化因子-趋化因子受体系统介导的自分泌或旁分泌机制促进自身生长。

项目成果

Yamaguchi K, Itoh Y, et al.: "Engineered long terminal repeats of retroviral vectors nhance transgene expression in hepatocytes in vitro and in vivo"Mol Ther. 8(5). 796-803 (2003)

Yamaguchi K、Itoh Y 等人：“工程化的逆转录病毒载体长末端重复序列可增强体外和体内肝细胞中的转基因表达”Mol Ther。

Kasahara A, Itoh Y, et al.: "Interferon treatment improves survival in chronic hepatitis C patients showing biochemical"J Viral Hepat. 11(2). 148-156 (2004)

Kasahara A、Itoh Y 等人：“干扰素治疗可提高显示生化特征的慢性丙型肝炎患者的生存率”J Viral Hepat。

Chemokine CCL20 enhances the growth of HuH7 cells via phosphorylation of p44/42 MAPK in vitro

• DOI: 10.1016/j.bbrc.2004.07.207
• 发表时间: 2004-09-24
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Fujii, H;Itoh, Y;Okanoue, T
• 通讯作者: Okanoue, T

Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to the interferon therapy

对干扰素治疗持续有效后发展为肝细胞癌的慢性丙型肝炎患者的特征

• 发表时间: 2004
• 期刊: Cancer 101
• 作者: Makiyama A;et al.
• 通讯作者: et al.

Engineered long terminal repeats of retroviral vectors enhance transgene expression in hepatocytes in vitro and in vivo.

• DOI: 10.1016/j.ymthe.2003.08.005
• 发表时间: 2003-11
• 期刊: Molecular therapy : the journal of the American Society of Gene Therapy
• 作者: K. Yamaguchi;K. Itoh;N. Ohnishi;Y. Itoh;C. Baum;T. Tsuji;Toshikazu Nagao;H. Higashitsuji;T. Okanoue;J. Fujita