Differentiation of liver cancer stem cells

肝癌干细胞的分化

• 批准号: 20599005
• 负责人: YAMASHITA Taro
• 金额: $ 2.48万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20599005/
• 关键词: 癌; 発生・分化; 幹細胞; マイクロアレイ; 発現制御; 肝細胞癌; Oncostatin M; 抗癌剤感受性; 細胞周期; アポトーシス; 肝細胞分化シグナル; 抗癌剤抵抗性; Wntシグナル

Recent evidence suggests that tumor cells possess stem cell features (cancer stem cells) to self-renew and give rise to relatively differentiated cells through asymmetric division, thereby forming heterogeneous populations. Cancer stem cells are considered to be resistant to chemotherapy and radiotherapy, which might be associated with the recurrence of the tumor after treatment. Oncostatin M (OSM) is a pleiotropic cytokine known to activate the hepatocytic differentiation program in hepatoblasts in an OSMR-specific manner. We identified that OSMR is expressed in a subset of liver cancer stem cells and OSM induces hepatocytic differentiation of these cells. OSM-mediated hepatocytic differentiation effectively suppressed HCC growth when combined with conventional chemotherapy, suggesting the utility of OSM for the treatment of liver cancer stem cells.

最近的证据表明，肿瘤细胞具有干细胞功能(肿瘤干细胞)可以自我更新，并通过不对称分裂产生相对分化的细胞，从而形成异质群体。肿瘤干细胞被认为对化疗和放疗具有耐药性，这可能与肿瘤治疗后的复发有关。OSM是一种多效性细胞因子，能以OSMR特异性的方式激活肝母细胞的肝细胞分化程序。我们发现OSMR在肝癌干细胞亚群中有表达，OSM可诱导这些细胞向肝细胞分化。OSM介导的肝细胞分化与常规化疗联合应用可有效抑制肝癌生长，提示OSM可用于肝癌干细胞的治疗。

项目成果

Signaling pathways responsible for self-renewal and differentiation in liver cancer stem cells.

负责肝癌干细胞自我更新和分化的信号通路。

• 发表时间: 2010
• 作者: Yamashita T;Honda M;Kaneko S.
• 通讯作者: Kaneko S.

In : Molecular Genetics of Liver Neoplasia.(Chapter 16.Heterogeneity of Liver Cancer Stem Cells.)

见：肝肿瘤的分子遗传学。（第 16 章肝癌干细胞的异质性。）

• 发表时间: 2010
• 作者: Yamashita T;et al.
• 通讯作者: et al.

Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells.

• DOI: 10.1002/hep.22989
• 发表时间: 2009-08
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Ji, Junfang;Yamashita, Taro;Budhu, Anuradha;Forgues, Marshonna;Jia, Hu-Liang;Li, Cuiling;Deng, Chuxia;Wauthier, Elaine;Reid, Lola M.;Ye, Qing-Hai;Qin, Lun-Xiu;Yang, Wen;Wang, Hong-Yang;Tang, Zhao-You;Groce, Carlo M.;Wang, Xin Wei
• 通讯作者: Wang, Xin Wei

EpCAM^+ hepatocellular carcinoma cells are tumor initiating t.ells with stem/progenitor cell features

EpCAM^肝细胞癌细胞是具有干/祖细胞特征的肿瘤起始细胞

• 发表时间: 2009
• 期刊: Gastroenterology 136
• 作者: Yamashita T.;他15名
• 通讯作者: 他15名

Comprehensive gene expression analysis of 5′-end of mRNA identified novel intronic transcripts associated with hepatocellular carcinoma

• DOI: 10.1016/j.ygeno.2010.01.004
• 发表时间: 2010-04-01
• 期刊: GENOMICS
• 影响因子: 4.4
• 作者: Hodo, Yuji;Hashimoto, Shin-ichi;Matsushima, Kouji
• 通讯作者: Matsushima, Kouji