Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma.
Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma.
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DOI：
10.1038/bjc.2014.151
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发表时间：
2014-04-29
影响因子：
8.8
通讯作者：
Morimoto, C.
中科院分区：
文献类型：
--
作者：
Yamamoto, J.;Ohnuma, K.;Hatano, R.;Okamoto, T.;Komiya, E.;Yamazaki, H.;Iwata, S.;Dang, N. H.;Aoe, K.;Kishimoto, T.;Yamada, T.;Morimoto, C.
恶性胸膜间皮瘤是一种侵袭性胸膜间皮瘤。CD 26分子优先表达于上皮样型MPM。本研究探讨了CD 26在体内外调控MPM细胞的分子机制。生物化学和细胞生物学方法被用于确定一个新的MPM的分子靶点。还使用动物模型评估了其对肿瘤扩张的贡献。还评估了MPM的临床样品的表达。我们确定MPM中的细胞生长抑制作用是由生长抑素（SST）受体4（SSTR 4）介导的，受到CD 26分子相互作用的抑制。我们还表明，SSTR 4介导的细胞生长抑制作用由SHP-2 PTP调节，并且SST激动剂的这种抑制作用通过抗CD 26抗体交联后相关分子的脂筏聚集而增强。最后，使用体内异种移植模型，我们证明了抗CD 26 mAb与SSTR 4激动剂治疗联合使用时的抗肿瘤作用增强，并且SSTR 4与从患者手术标本中获得的上皮样或双相型MPM组织上的CD 26高度共表达。因此，人源化抗CD 26 mAb和SSTR 4激动剂的联合治疗可能增强对MPM的抗肿瘤作用。
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from mesothelial lining of pleura. CD26 molecules preferentially expressed on epithelioid type of MPM. This study investigates the molecular mechanisms of CD26 regulating MPM cells in vitro and in vivo. Biochemical and cell biological approaches were used for identifying a novel molecular target of MPM. Its contribution to tumour expansion has been also assessed using animal models. The clinical samples of MPM were also assessed for its expression. We identify that cytostatic effects in MPM are mediated by somatostatin (SST) receptor 4 (SSTR4), being inhibited by the interaction of CD26 molecules. We also indicates that SSTR4-mediated cytostatic effects are regulated by SHP-2 PTP, and that this inhibitory effect by SST agonist is enhanced via lipid raft clustering of associated molecules following crosslinking of anti-CD26 antibody. Finally, using an in vivo xenograft model, we demonstrate that the anti-tumour effect of anti-CD26 mAb is enhanced when combined with SSTR4 agonist treatment, and that SSTR4 is highly coexpressed with CD26 on epithelioid or biphasic types of MPM tissues obtained from patients' surgical specimens. Combination therapy with humanised anti-CD26 mAb and SSTR4 agonist may therefore potentiate anti-tumour effect on MPM.
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影响因子：
3.7
作者：
Okamoto T;Iwata S;Yamazaki H;Hatano R;Komiya E;Dang NH;Ohnuma K;Morimoto C
通讯作者：
Morimoto C
影响因子：
11.5
作者：
Inamoto, Teruo;Yamochi, Tadanori;Morimoto, Chikao
通讯作者：
Morimoto, Chikao
膀胱出口梗阻患者前列腺组织中生长抑素受体亚型的免疫组织化学检测和定位。
DOI：
10.3233/clo-2008-0433
发表时间：
2008
期刊：
Cellular oncology : the official journal of the International Society for Cellular Oncology
影响因子：
--
作者：
Montironi R;Cheng L;Mazzucchelli R;Morichetti D;Stramazzotti D;Santinelli A;Moroncini G;Galosi AB;Muzzonigro G;Comeri G;Lovisolo J;Cosciani-Cunico S;Bono AV
通讯作者：
Bono AV
影响因子：
6.4
作者：
Ohnuma, K;Ishii, T;Morimoto, C
通讯作者：
Morimoto, C
影响因子：
4.8
作者：
Beck, M;Brickley, K;Stephenson, FA
通讯作者：
Stephenson, FA