Association of deubiquitin ligase and cell surface molecules regulates the pathophysiology of malignant pleural mesothelioma

去泛素连接酶和细胞表面分子的关联调节恶性胸膜间皮瘤的病理生理学

• 批准号: 24659401
• 负责人: MORIMOTO Chikao
• 金额: $ 2.33万
• 依托单位: Juntendo University
• 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-24659401/
• 关键词: 悪性中皮腫; CD26; CD9; α5β1インテグリン; ペリオスチン; ソマトスタチン受容体４（SSTR4）; 脱ユビキチン酵素22（USP22）; 浸潤転移; SSTR4; CD26抗体; SHP-2; 細胞増殖; アゴニスト; USP22; 脱ユビキチン酵素; β1インテグリン; β1α5

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. CD26 potentiates tumor cell invasion through its interaction with alpha5 beta1 integrin, and CD9 negatively regulates tumor cell invasion by reducing the level of CD26-alpha5 beta1 integrin complex through an inverse correlation between CD9 and CD26 expression. We also showed CD26 associated with somatostatin (SST) receptor 4 and this interaction regulates the growth of MPM cells. Moreover, CD26 is also associated with deubiquitin ligase22 (USP22) which regulated the invasion and metastasis of CD26 positive mesothelioma cells and actually these molecules colocalized in the tissue samples of malignant mesothelioma.

恶性胸膜间皮瘤（MPM）是一种起源于胸膜间皮层的侵袭性恶性肿瘤。它通常与石棉接触史有关，预后很差。我们发现CD26的表达上调MPM细胞的骨膜蛋白分泌，导致MPM细胞迁移和侵袭活性增强。CD26通过与alpha5 beta1整合素的相互作用增强肿瘤细胞的侵袭，CD9通过CD9与CD26表达呈负相关关系，降低CD26-alpha5 beta1整合素复合物的水平，负向调节肿瘤细胞的侵袭。我们还发现CD26与生长抑素（SST）受体4相关，这种相互作用调节MPM细胞的生长。此外，CD26还与调节CD26阳性间皮瘤细胞侵袭和转移的去泛素连接酶22 （deubiquitin ligase22, USP22）相关，实际上这些分子在恶性间皮瘤组织样本中存在共定位。

项目成果

MERSコロナウイルス感染予防治療剤

MERS冠状病毒感染预防和治疗剂

• 发表时间: 2013

Humanized anti-CD26 mAb Leads to Prophylaxis and Treatment of GVHD in Hu-PBL-NOG Model Mice.

人源化抗 CD26 mAb 可预防和治疗 Hu-PBL-NOG 模型小鼠的 GVHD。

• 发表时间: 2012
• 作者: Hatano R; Morimoto C;et al.
• 通讯作者: et al.

CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma.

• DOI: 10.3892/or.2012.2116
• 发表时间: 2013-01
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Amatya VJ;Takeshima Y;Aoe K;Fujimoto N;Okamoto T;Yamada T;Kishimoto T;Morimoto C;Inai K
• 通讯作者: Inai K

抗ヒト化CD26モノクローナル抗体又はその抗原結合性断片

抗人源化CD26单克隆抗体或其抗原结合片段

• 发表时间: 2013

Inhibition of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection by Anti-CD26 Monoclonal Antibody.

抗 CD26 单克隆抗体抑制中东呼吸综合征冠状病毒 (MERS-CoV) 感染。

• 发表时间: 2013
• 期刊: J Virol.
• 作者: Ohnuma K;Haagmans BL;Hatano R;Raj VS;Mou H;Iwata S;Dang NH;Bosch BJ;Morimoto C.
• 通讯作者: Morimoto C.