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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Sprache:eng
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Zusammenfassung: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.
ISSN:0903-1936
1399-3003
DOI:10.1183/13993003.01610-2017