The development of novel therapeutic strategies for targeting ovarian cancer stem cells

针对卵巢癌干细胞的新型治疗策略的开发

• 批准号: 21390454
• 负责人: KATABUCHI Hidetaka
• 金额: $ 11.32万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390454/
• 关键词: 上皮性卵巣癌; 癌幹細胞; 卵巣表層上皮; 卵巣癌治療; 卵巣癌モデル

Emerging evidence suggests that human cancers arise from normal stem cells, and are composed of hierarchies of cells sustained by tumor-initiating cells(T-ICs), conceptually termed cancer stem cells(CSCs). Epithelial cell adhesion molecule(EpCAM) is a type I transmembrane glycoprotein that is expressed specifically in epithelial tissues and is overexpressed in some epithelial cancers. In normal tissues, EpCAM is expressed in several types of epithelial stem/progenitor cells and contributes to tissue development. On the other hand, a subpopulation of EpCAM-positive cells has been identified as CSCs in some human cancers. In the light of these considerations, we evaluated the EpCAM-positive cells for their stem cell properties in adult mouse ovary, and established the ovarian T-ICs by introduction of defined genetic elements in EpCAM-positive cells. EpCAM-positive cells possess the hallmarks of somatic stem cells and CSCs in this mouse model of ovarian tumorigenesis. Furthermore, our experimental mouse model facilitates further studies toward a comprehensive understanding of normal stem cells and CSCs in ovary. Ultimately, such studies will be imperative to define whether eradication of ovarian CSCs is critical for effective therapy.

新出现的证据表明，人类癌症起源于正常的干细胞，由肿瘤启动细胞（t - ic）维持的细胞层次组成，概念上称为癌症干细胞（CSCs）。上皮细胞粘附分子（Epithelial cell adhesion molecule, EpCAM）是一种I型跨膜糖蛋白，在上皮组织中特异性表达，在一些上皮癌中过表达。在正常组织中，EpCAM在几种类型的上皮干细胞/祖细胞中表达，并有助于组织发育。另一方面，epcam阳性细胞亚群已被确定为某些人类癌症中的CSCs。基于这些考虑，我们在成年小鼠卵巢中评估了epcam阳性细胞的干细胞特性，并通过在epcam阳性细胞中引入定义的遗传元件建立了卵巢t - ic。epcam阳性细胞在卵巢肿瘤发生小鼠模型中具有体细胞干细胞和CSCs的特征。此外，我们的实验小鼠模型有助于进一步研究卵巢正常干细胞和CSCs的全面认识。最终，这样的研究将是必要的，以确定根除卵巢csc是否对有效治疗至关重要。

项目成果

Short RNA duplexes elicit RIG-1-mediated apoptosis in a cell type- and length-dependent manner

短RNA双链体以细胞类型和长度依赖性方式引发RIG-1介导的细胞凋亡

• 发表时间: 2011
• 期刊: Science Signaling
• 影响因子: 7.3
• 作者: Ishibashi O;et al
• 通讯作者: et al

CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth

• DOI: 10.1016/j.ccr.2011.01.038
• 发表时间: 2011-03-15
• 期刊: CANCER CELL
• 影响因子: 50.3
• 作者: Ishimoto, Takatsugu;Nagano, Osamu;Saya, Hideyuki
• 通讯作者: Saya, Hideyuki

Mutual contribution of Pten and estrogen to endometrial carcinogenesis in a PtenloxP/loxP mouse model

PtenloxP/loxP 小鼠模型中 Pten 和雌激素对子宫内膜癌发生的相互影响

• 发表时间: 2011
• 期刊: Int J Gynecol Cancer
• 影响因子: 4.8
• 作者: F. Saito;H. Tashiro;Y. To;H. Ohtake;T. Ohba;A. Suzuki;H. Katabuchi
• 通讯作者: H. Katabuchi

Long-term oncological outcomes of ovarian serous carcinomas with psammoma bodies : a novel insight to the molecular pathogenesis of ovarian epithelial carcinoma.

卵巢浆液性癌与砂粒体的长期肿瘤学结果：对卵巢上皮癌分子发病机制的新见解。

• 发表时间: 2010
• 期刊: Cancer Science
• 影响因子: 5.7
• 作者: T.Motohara;H.Tashiro;et al.
• 通讯作者: et al.

Special lecture「A new tool to investigate the tumorigenesis and therapeutic modalities of epithelial ovarian cancer」

特别讲座“研究上皮性卵巢癌肿瘤发生和治疗方式的新工具”

• 发表时间: 2009
• 作者: Ogata;S.;Morishige;K.;Sawada;K.;Hashimoto;K.;Mabuchi;S.;Kawase;C.;Ooyagi;C.;Sakata;M.;Kimura;T.;H. Katabuchi
• 通讯作者: H. Katabuchi