Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma
Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma
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DOI：
10.1183/13993003.01610-2017
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发表时间：
2018-05
影响因子：
24.3
通讯作者：
T. Otsuki;Taku Nakashima;H. Hamada;Yusuke Takayama;Shin Akita;T. Masuda;Y. Horimasu;S. Miyamoto;H. Iwamoto;K. Fujitaka;Y. Miyata;M. Miyake;N. Kohno;M. Okada;N. Hattori
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文献类型：
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作者：
T. Otsuki;Taku Nakashima;H. Hamada;Yusuke Takayama;Shin Akita;T. Masuda;Y. Horimasu;S. Miyamoto;H. Iwamoto;K. Fujitaka;Y. Miyata;M. Miyake;N. Kohno;M. Okada;N. Hattori
血管生成是恶性胸膜间皮瘤（MPM）发展的关键因素，抗血管生成策略可能对MPM有效。氨肽酶N (APN)/CD13促进肿瘤血管生成并与不良预后相关；然而，其在MPM中的临床意义尚不清楚。在37例连续手术切除的MPM患者中，我们评估了切除肿瘤中免疫组织化学APN/CD13表达与生存之间的关系。此外，在小鼠原位植入EHMES-10（丰富表达APN/CD13）和msto211h（几乎不表达APN/CD13） MPM细胞中，研究了完全人源化抗APN/CD13单克隆抗体MT95-4的抗肿瘤和抗血管生成作用。肿瘤APN/CD13高表达与MPM患者预后不良相关（p=0.04）， MT95-4治疗可降低携带ehms -10细胞的小鼠的肿瘤生长和血管生成，但对m斯托- 211h细胞没有作用。此外，在携带ehms -10细胞的小鼠中，MT95-4联合顺铂比单用顺铂更有效地抑制肿瘤进展。综上所述，这些结果表明APN/CD13与MPM的侵袭性有关。在这里，MT95-4治疗可能通过抑制血管生成来减少肿瘤进展，这表明APN/CD13是MPM治疗的潜在分子靶点。此外，MT95-4和顺铂联合治疗可能是治疗APN/CD13高表达MPM的一种有希望的方法。氨肽酶N (APN)/CD13是间皮瘤中APN/CD13高表达的潜在治疗靶点http://ow.ly/dzmu30iGKzd
Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM) and antiangiogenic strategies might be effective against MPM. Aminopeptidase N (APN)/CD13 promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear. In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanised anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells. High tumour APN/CD13 expression was associated with poor prognosis in MPM patients (p=0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10 but not MSTO-211H cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone. Taken together, these results suggest that APN/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression. Aminopeptidase N (APN)/CD13 is a potential therapeutic target in mesothelioma exhibiting high APN/CD13 expression http://ow.ly/dzmu30iGKzd