RT Journal Article
SR Electronic
T1 Aminopeptidase N/CD13 as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1701610
DO 10.1183/13993003.01610-2017
A1 Takahiko Otsuki
A1 Taku Nakashima
A1 Hironobu Hamada
A1 Yusuke Takayama
A1 Shin Akita
A1 Takeshi Masuda
A1 Yasushi Horimasu
A1 Shintaro Miyamoto
A1 Hiroshi Iwamoto
A1 Kazunori Fujitaka
A1 Yoshihiro Miyata
A1 Masayuki Miyake
A1 Nobuoki Kohno
A1 Morihito Okada
A1 Noboru Hattori
YR 2018
UL http://erj.ersjournals.com/content/early/2018/03/01/13993003.01610-2017.abstract
AB Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM), and antiangiogenic strategies might be effective against MPM. Aminopeptidase N/CD13 (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 humanized 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 suggested 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 is a potential therapeutic target in mesothelioma exhibiting high Aminopeptidase N expression.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Otsuki has nothing to disclose.Conflict of interest: Dr. Nakasihma has nothing to disclose.Conflict of interest: Dr. Hamada has nothing to disclose.Conflict of interest: Dr. Takayama has nothing to disclose.Conflict of interest: Dr. Akita has nothing to disclose.Conflict of interest: Dr. Masuda has nothing to disclose.Conflict of interest: Dr. Horimasu has nothing to disclose.Conflict of interest: Dr. Miyamoto has nothing to disclose.Conflict of interest: Dr. Iwamoto has nothing to disclose.Conflict of interest: Dr. Fujitaka has nothing to disclose.Conflict of interest: Dr. Miyata has nothing to disclose.Conflict of interest: Dr. Miyake has nothing to disclose.Conflict of interest: Dr. Kohno has nothing to disclose.Conflict of interest: Dr. Okada has nothing to disclose.Conflict of interest: Dr. Hattori has nothing to disclose.