Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma

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...

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Veröffentlicht in:The European respiratory journal 2018-05, Vol.51 (5), p.1701610-1701610
Hauptverfasser: Otsuki, Takahiko, Nakashima, Taku, Hamada, Hironobu, Takayama, Yusuke, Akita, Shin, Masuda, Takeshi, Horimasu, Yasushi, Miyamoto, Shintaro, Iwamoto, Hiroshi, Fujitaka, Kazunori, Miyata, Yoshihiro, Miyake, Masayuki, Kohno, Nobuoki, Okada, Morihito, Hattori, Noboru
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container_issue 5
container_start_page 1701610
container_title The European respiratory journal
container_volume 51
creator Otsuki, Takahiko
Nakashima, Taku
Hamada, Hironobu
Takayama, Yusuke
Akita, Shin
Masuda, Takeshi
Horimasu, Yasushi
Miyamoto, Shintaro
Iwamoto, Hiroshi
Fujitaka, Kazunori
Miyata, Yoshihiro
Miyake, Masayuki
Kohno, Nobuoki
Okada, Morihito
Hattori, Noboru
description 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.
doi_str_mv 10.1183/13993003.01610-2017
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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. 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source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Aminopeptidase
Angiogenesis
Antiangiogenic agents
CD13 antigen
Cisplatin
Medical prognosis
Mesothelioma
Monoclonal antibodies
Patients
Prognosis
Therapeutic applications
Tumors
title Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma
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