Human Peritoneal Mesothelial Cell play important roles in the development of peritoneal metastasis by its EMT change

人腹膜间皮细胞通过EMT变化在腹膜转移的发生发展中发挥重要作用

• 批准号: 22591451
• 负责人: FUSHIDA Sachio
• 金额: $ 2.41万
• 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: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591451/
• 关键词: 胃癌; 腹膜播種; 腹膜中皮細胞; EMT; 微小環境; 形質 転換 (EMT); TGFβ; パクリタキセル; fibrocyte; 胃癌腹膜播種; 形質転換; 線維化; paclitaxel; TGF-β

We investigated whether TGF-β derived from cancer cells in the peritoneal microenvironment activates human peritoneal mesothelial cells (HPMCs), leading to the progression and fibrosis of gastric cancer. We found that activated HPMCs (a-HPMCs) became more invasive and up-regulated proliferation of human gastric cancer-derived MKN45 cells following direct cell-cell contact. These EMT-like changesof HPMC were suppressed under 5nM of paclitaxel pretreatment by inhibiting Smad2 phosphorylation. To measure the effects of co-culture in vivo, we developed a mouse xenograft model. The largest tumors were observed in mice given MKN45 cells that had been co-cultured with a-HPMCs. Additionaly, these tumors contained HPMC-derived fibrous tissue.

我们研究了来源于腹膜微环境中的癌细胞的TGF-β是否激活人腹膜间皮细胞（HPMCs），从而导致胃癌的进展和纤维化。我们发现活化的HPMCs（a-HPMCs）在细胞-细胞直接接触后变得更具侵袭性并且上调人胃癌衍生的MKN 45细胞的增殖。5 nM紫杉醇预处理可通过抑制Smad 2磷酸化而抑制HPMC的EMT样改变。为了测量体内共培养的效果，我们开发了小鼠异种移植模型。在给予与a-HPMC共培养的MKN 45细胞的小鼠中观察到最大的肿瘤。此外，这些肿瘤含有HPMC衍生的纤维组织。

项目成果

Interaction of gastric cancer cell and bone-marrow derived mesenchymal cell; fibrocyte

胃癌细胞与骨髓间充质细胞的相互作用；

• 发表时间: 2011
• 作者: Maruyama T;Kawaguchi Y;Kono K;Miyazaki T;Fushida S
• 通讯作者: Fushida S

スキルス胃癌の病態と集学的治療の現況と将来展望

硬质胃癌病理生理学及多学科治疗的现状与展望

• 发表时间: 2013
• 作者: 安永正浩;眞鍋史乃;松村保広;伏田幸夫他
• 通讯作者: 伏田幸夫他

腹腔内微小環境下における線維化メカニズムの解明とその制御

腹膜内微环境纤维化机制及其控制的阐明

• 发表时间: 2012
• 作者: Miyazaki T;Inose T;Tanaka N;Suzuki S;Hara K;Ozawa D;Yokobori T;Sakai M;Souda M;Fukuchi M;Kuwano H.;安永正浩;Inoue M;伏田幸夫;Sano A;安永正浩;Kono K;伏田幸夫他
• 通讯作者: 伏田幸夫他

Analysis of mesenchymal transition of human peritoneal mesothelial cell and cell-cell interaction with gastric cancer cell in the microenvironment of peritoneal metastasis

腹膜转移微环境中人腹膜间皮细胞间质转化及与胃癌细胞相互作用的分析

• 发表时间: 2010
• 作者: Komiyama H;Miyake K;Asai K;Mizuno K;Shimada T;安永正浩;Kosaku Mimura;Fushida S
• 通讯作者: Fushida S

スキルス胃癌 基礎と臨床

硬质胃癌的基础与临床

• 发表时间: 2010
• 作者: Liem;I. K.;Yamaguchi;M.;Aoyama;H.;米村豊・遠藤良夫・三浦真弘
• 通讯作者: 米村豊・遠藤良夫・三浦真弘