Analysis of biological characteristic features in cancer stem cell in digestive organs

消化器官肿瘤干细胞生物学特性分析

• 批准号: 20590809
• 负责人: HIGUCHI Hajime
• 金额: $ 2.91万
• 依托单位: Keio 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-20590809/
• 关键词: 癌幹細胞; epithelial-to-mesenchymal transition; apoptosis; mesenchymal stem cell; アポトーシス; EMT; side population; Spheroid; FMT

Cancer related materials, i.e., cell lines, endoscopic biopthy specimen, or, surgically resected specimen, were analyzed for ; i) expression of cancer stem cell markers, ii) tumor formation, iii) colony forming activity, iv) drug-resistance, and v) potentials for local invasion and metastasis. Our results suggest that side population (SP) cells isolated from pancreatic cancer have some cancer stem cell-like properties ; i) high tumorigenic/colony forming activity, ii) resistance to some chemotherapeutic drugs as well as apoptosis-inducing molecules such as TRAIL, iii) high metstatic potential, and iv) enhanced capability to undergo epithelial-to-mesenchymal transition (EMT) and invasion. In hepatocellular carcinoma, CD133-positive side population cells were highly tumorigenic and chemotherapy-resistant. These cancer stem cell-like features were enhanced by co-culturing with bone marrow-derived mesenchymal stem cells (MSCs) and/or MSC-derived myofibroblast-like cells, suggesting MSCs provide microenvironment so-called cancer stem cell niche to maintain stem cell phenotype in cancer derived SP cells. These results suggest that SP cells would be a therapeutic tagrget, especially to prevent cancer sten cell invasion and metastasis. Mesenchymal cell-derived microenvironment would be another terapeutic target to regulate cancer stem cell maintenance.

癌症相关材料，即，分析细胞系、内窥镜活检样本或手术切除样本的：i）癌症干细胞标志物的表达，ii）肿瘤形成，iii）集落形成活性，iv）耐药性，和v）局部侵袭和转移的可能性。我们的研究结果表明，从胰腺癌中分离的侧群（SP）细胞具有一些癌症干细胞样特性; i）高致瘤性/集落形成活性，ii）对某些化疗药物以及肿瘤诱导分子（如TRAIL）的抗性，iii）高转移潜力，以及iv）增强的经历上皮向间充质转化（EMT）和侵袭的能力。在肝细胞癌中，CD 133阳性侧群细胞具有高度致瘤性和化疗耐药性。这些癌症干细胞样特征通过与骨髓来源的间充质干细胞（MSC）和/或MSC来源的肌纤维母细胞样细胞共培养而增强，这表明MSC提供了所谓的癌症干细胞小生境的微环境以维持癌症来源的SP细胞中的干细胞表型。提示SP细胞有可能成为一种治疗靶点，特别是在预防肿瘤干细胞侵袭和转移方面。间充质细胞来源的微环境将是调节肿瘤干细胞维持的另一个靶点。

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DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8

• DOI: 10.1111/j.1349-7006.2010.01565.x
• 发表时间: 2010-06-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Kurita, Satoshi;Higuchi, Hajime;Hibi, Toshifumi
• 通讯作者: Hibi, Toshifumi

Side population of pancreatic cancer cells predominates in TGF-beta-me diated epithelial to mesenchymal transition and invasion

胰腺癌细胞的侧群在 TGF-β 介导的上皮间质转化和侵袭中占主导地位

• 发表时间: 2009
• 期刊: International Journal of Cancer 124
• 作者: Kabashima A;et al.
• 通讯作者: et al.

Wnt signaling contributes to the maintenance of cancer stem cell-like populations in Huh7 hepatocellular carcinoma cell line : Role of hepatic stellate cells.

Wnt 信号传导有助于 Huh7 肝细胞癌细胞系中癌症干细胞样群的维持：肝星状细胞的作用。

• 发表时间: 2010
• 作者: Masayuki Adachi;Hajime Higuchi;Ayano Kabashima;Shinsuke Funakoshi;Shoko Nakamura;Hiromasa Takaishi;Toshifumi Hibi
• 通讯作者: Toshifumi Hibi

Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion.

胰腺癌细胞的侧群在 TGF-β 介导的上皮间质转化和侵袭中占主导地位。

• 发表时间: 2009
• 期刊: Int-J-Cancer 124
• 作者: Ayano Kabashima;Hajime Higuchi;Hiromasa Takaishi;Yumi Matsuzaki;Sadafumi Suzuki;Motoko Izumiya;Hideko Iizuka;Gen Sakai;Shigenari Hozawa;Toshifumi Azuma;Toshifumi Hibi
• 通讯作者: Toshifumi Hibi