Identification and characterization of hepatic cancer stem cells using oncogene-regulatory expressing transgenic mice

使用表达癌基因调节的转基因小鼠鉴定和表征肝癌干细胞

• 批准号: 20790951
• 负责人: ISHII Takamichi
• 金额: $ 2.75万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790951/
• 关键词: 肝臓外科学; 癌幹細胞; 肝細胞癌; 胆管細胞癌

that CSCs have self-renewal activities and multipotencies, which display a hierarchy in tumor tissues. This study aimed to demonstrate that alpha-fetoprotein (AFP)-producing cells in cholangiocarcinomas (CC) possessed CSC-like properties. The transgene vector that contained enhanced green fluorescent protein (EGFP) under the control of the human AFP enhancer/promoter was transfected into human CC cell lines. The AFP-EGFP-positive cells in RBE had self-renewal activity, differentiation ability, and tumorigenicity. The Notch signaling pathway was suggested to play an important role to maintain the stemness of the AFP-EGFP-positive cells. In addition, in order to explore the origin of CSCs, we successfully generated oncogene-regulatory expressing transgenic mice. One cell line was obtained from only fetal hepatocytes derived from the transgenic mice, thus suggesting that CSCs were generated from transformed stem cells.

CSCs具有自我更新活性和多能性，在肿瘤组织中表现出层次结构。本研究旨在证明胆管癌 (CC) 中产生甲胎蛋白 (AFP) 的细胞具有 CSC 样特性。将含有在人 AFP 增强子/启动子控制下的增强型绿色荧光蛋白 (EGFP) 的转基因载体转染到人 CC 细胞系中。 RBE中的AFP-EGFP阳性细胞具有自我更新活性、分化能力和致瘤性。 Notch信号通路被认为在维持AFP-EGFP阳性细胞的干细胞性方面发挥着重要作用。此外，为了探索CSC的起源，我们成功生成了表达癌基因调节的转基因小鼠。仅从转基因小鼠的胎儿肝细胞中获得了一种细胞系，因此表明CSC是由转化的干细胞产生的。

项目成果

ALPHA-FETOPROTEIN PRODUCING CELLS AS A CANDIDATE FOR CANCER STEM CELLS OF CHOLANGIOCELLULAR CARCINOMA

产生α-胎蛋白的细胞作为胆管细胞癌癌症干细胞的候选者

• 发表时间: 2009
• 作者: Takamichi Ishii;Kentaro Yasuchika;Ken Fukumitsu;Sayuri Konishi;Masatoshi Kajiwara;Ryo Kamimura;Naoya Sasaki;Hirofumi Suemori;Norio Nakatsuji;Iwao Ikai;Shinji Uemoto
• 通讯作者: Shinji Uemoto

上本伸二「胆管癌における癌幹細胞としてのAFP産生細胞」

Shinji Uemoto“胆管癌中产生 AFP 的细胞作为癌症干细胞”

• 发表时间: 2008
• 作者: 石井隆道;安近健太郎;福光剣;末盛博文;中辻憲夫;猪飼伊和夫
• 通讯作者: 猪飼伊和夫

胆管癌においてAFP産生細胞は癌幹細胞の特徴を持つ

胆管癌中产生AFP的细胞具有癌症干细胞的特征

• 发表时间: 2008
• 作者: 石井隆道;安近健太郎;末盛博文;中辻憲夫;猪飼伊和夫;上本伸二
• 通讯作者: 上本伸二

In vitro hepatic maturation of human embryonic stem cells by using a mesenchymal cell line derived from murine fetal livers

• DOI: 10.1007/s00441-009-0906-7
• 发表时间: 2010-03-01
• 期刊: CELL AND TISSUE RESEARCH
• 影响因子: 3.6
• 作者: Ishii, Takamichi;Yasuchika, Kentaro;Nakatsuji, Norio
• 通讯作者: Nakatsuji, Norio

ALPHA-FETOPROTEIN-PRODUCING CELLS ACT AS CANCER STEM CELLS IN HUMAN PANCREATIC CANCER

产生α-胎蛋白的细胞在人类胰腺癌中充当癌症干细胞

• 发表时间: 2010
• 作者: Sasaki N;et al
• 通讯作者: et al