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特征（癌症干细胞），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。癌症干细胞被认为对化疗和放疗具有抵抗力，这可能与治疗后肿瘤的复发有关。制瘤素 M (OSM) 是一种多效细胞因子，已知能以 OSMR 特异性方式激活成肝细胞中的肝细胞分化程序。我们发现 OSMR 在肝癌干细胞的子集中表达，并且 OSM 诱导这些细胞的肝细胞分化。当与传统化疗结合时，OSM介导的肝细胞分化有效抑制HCC生长，表明OSM可用于治疗肝癌干细胞。

项目成果

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.

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

Application of Serial Analysis of Gene Expression in Cancer Research

• DOI: 10.2174/138920108785915102
• 发表时间: 2008-10-01
• 期刊: CURRENT PHARMACEUTICAL BIOTECHNOLOGY
• 影响因子: 2.8
• 作者: Yamashita, T.;Honda, M.;Kaneko, S.
• 通讯作者: Kaneko, S.

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.

EpCAM^+ hepatocellular carcinoma cells are tumor initiating cells 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