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

Eur Respir J. 2018 May 24;51(5):1701610. doi: 10.1183/13993003.01610-2017. Print 2018 May.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • CD13 Antigens / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Female
  • Humans
  • Male
  • Mesothelioma / drug therapy*
  • Mice, Inbred BALB C
  • Mice, SCID
  • Middle Aged
  • Molecular Targeted Therapy*
  • Multivariate Analysis
  • Neovascularization, Pathologic / drug therapy
  • Pleural Neoplasms / drug therapy*
  • Xenograft Model Antitumor Assays


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • CD13 Antigens
  • Cisplatin