Cancer stem cell for peritoneal metastasis in abdominal cavity

癌症干细胞用于腹腔腹膜转移

• 批准号: 24659600
• 负责人: ISHIGAMI Hironori
• 金额: $ 2.25万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659600/
• 关键词: 腹膜播種; 幹細胞; フローサイトメトリー; 腹腔; FACS

We found that a minor subset of human intraperitoneal free cells with CD90+CD45- displayed the characteristics of mesenchymal stem cell, and differentiated into myofibroblast by the stimulation with TGFb, and intraperitoneal coinjection of with MKN45 significantly enhanced the rate of metastatic formation in the peritoneum of nude mice. Histological examination revealed that many MSC were engrafted in metastatic nodules and were mainly located at the fibrous area. Dasatinib, a tyrosine kinase inhibitor, strongly inhibited the proliferation of MSC but not MKN45 in vitro. Nevertheless, oral administration of Dasatinib significantly inhibited the development of peritoneal metastasis of MKN45, and resulted in reduced fibrillar formation of metastatic nodules. The rate of CD326+ tumor cells measured with FACS could be a reliable diagnostic biomarker to determine the severity of peritoneal metastasis as well as effectiveness of chemotherapy.

结果发现，一小部分CD 90 + CD 45-的人腹腔游离细胞具有间充质干细胞的特性，在TGF β刺激下可分化为肌成纤维细胞，腹腔注射MKN 45可显著提高裸鼠腹膜转移的形成率。组织学检查发现，许多MSC在转移结节中植入，主要位于纤维区。酪氨酸激酶抑制剂达沙替尼在体外强烈抑制MSC的增殖，但不抑制MKN 45。然而，口服达沙替尼显著抑制了MKN 45腹膜转移的发展，并导致转移性结节的纤维形成减少。流式细胞术检测CD 326+肿瘤细胞率可作为判断腹膜转移严重程度和化疗有效性的可靠诊断生物标志物。

项目成果

CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment.

• DOI: 10.1371/journal.pone.0086516
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kitayama J;Emoto S;Yamaguchi H;Ishigami H;Watanabe T
• 通讯作者: Watanabe T

胃癌腹膜播種の成立における腹腔内遊離間葉系幹細胞の役割とその臨床的意義

腹腔游离间充质干细胞在胃癌腹膜播散建立中的作用及其临床意义

• 发表时间: 2014
• 作者: 北山丈二;江本成伸;山口博紀;石神浩徳;渡邉聡明
• 通讯作者: 渡邉聡明

Role of the intraperitoneal fibrocytes on the development of peritoneal metastasi

腹膜内纤维细胞在腹膜转移发展中的作用

• 发表时间: 2013
• 作者: 北山丈二;江本成伸;山口博紀;石神浩徳;渡邉聡明
• 通讯作者: 渡邉聡明

Role of the intraperitoneal fibrocytes on the development of peritoneal

腹膜内纤维细胞对腹膜发育的作用

• 发表时间: 2013
• 作者: Nakano K;Watanabe M;Matsunari H;Matsuda T;Honda K;Maehara M;Kanai T;Hayashida G;Kobayashi M;Umeyama K;Fujishiro S;Mizukami Y;Nagaya M;Hanazono Y;Nagashima H.;北山丈二
• 通讯作者: 北山丈二