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 |
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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. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression.</description><identifier>ISSN: 0903-1936</identifier><identifier>EISSN: 1399-3003</identifier><identifier>DOI: 10.1183/13993003.01610-2017</identifier><identifier>PMID: 29519924</identifier><language>eng</language><publisher>England: European Respiratory Society Journals Ltd</publisher><subject>Aminopeptidase ; Angiogenesis ; Antiangiogenic agents ; CD13 antigen ; Cisplatin ; Medical prognosis ; Mesothelioma ; Monoclonal antibodies ; Patients ; Prognosis ; Therapeutic applications ; Tumors</subject><ispartof>The European respiratory journal, 2018-05, Vol.51 (5), p.1701610-1701610</ispartof><rights>Copyright ©ERS 2018.</rights><rights>Copyright European Respiratory Society Journals Ltd. May 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-1c64e2e50c8f1c69d8a40ab2142e7c838ffbda709a4264ef45badc29c77bc1513</citedby><cites>FETCH-LOGICAL-c444t-1c64e2e50c8f1c69d8a40ab2142e7c838ffbda709a4264ef45badc29c77bc1513</cites><orcidid>0000-0002-8686-551X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29519924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Otsuki, Takahiko</creatorcontrib><creatorcontrib>Nakashima, Taku</creatorcontrib><creatorcontrib>Hamada, Hironobu</creatorcontrib><creatorcontrib>Takayama, Yusuke</creatorcontrib><creatorcontrib>Akita, Shin</creatorcontrib><creatorcontrib>Masuda, Takeshi</creatorcontrib><creatorcontrib>Horimasu, Yasushi</creatorcontrib><creatorcontrib>Miyamoto, Shintaro</creatorcontrib><creatorcontrib>Iwamoto, Hiroshi</creatorcontrib><creatorcontrib>Fujitaka, Kazunori</creatorcontrib><creatorcontrib>Miyata, Yoshihiro</creatorcontrib><creatorcontrib>Miyake, Masayuki</creatorcontrib><creatorcontrib>Kohno, Nobuoki</creatorcontrib><creatorcontrib>Okada, Morihito</creatorcontrib><creatorcontrib>Hattori, Noboru</creatorcontrib><title>Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma</title><title>The European respiratory journal</title><addtitle>Eur Respir J</addtitle><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.</description><subject>Aminopeptidase</subject><subject>Angiogenesis</subject><subject>Antiangiogenic agents</subject><subject>CD13 antigen</subject><subject>Cisplatin</subject><subject>Medical prognosis</subject><subject>Mesothelioma</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Therapeutic applications</subject><subject>Tumors</subject><issn>0903-1936</issn><issn>1399-3003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpdkE1P3DAQhq2qiN0Cv6BSZakXLgGP7U3iI1o-WmkFF3roKZo4E-pVvrCdA_8eBxYOPc1o9Mw7o4ex7yAuAEp1CcoYJYS6EJCDyKSA4gtbL9NsGX9la2GEysCofMW-hbAXCdQKjtlKmg0YI_Wa_b3q3TBONEXXYCB-f7m9BsUxcOTTGGmIDjse_5HHieboLI_onyhyN_AeO_c04BD51NHsE9dTGBPbubHHU3bUYhfo7FBP2J_bm8ftr2z3cPd7e7XLrNY6ZmBzTZI2wpZt6k1TohZYS9CSCluqsm3rBgthUMtEtnpTY2OlsUVRW9iAOmHn77mTH59nCrHqXbDUdTjQOIcqeZEGyrzME_rzP3Q_zn5I3yUqBy2MKpdA9U5ZP4bgqa0m73r0LxWIajFffZiv3swvF4q09eOQPdc9NZ87H6rVK-Mnfaw</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Otsuki, Takahiko</creator><creator>Nakashima, Taku</creator><creator>Hamada, Hironobu</creator><creator>Takayama, Yusuke</creator><creator>Akita, Shin</creator><creator>Masuda, Takeshi</creator><creator>Horimasu, Yasushi</creator><creator>Miyamoto, Shintaro</creator><creator>Iwamoto, Hiroshi</creator><creator>Fujitaka, Kazunori</creator><creator>Miyata, Yoshihiro</creator><creator>Miyake, Masayuki</creator><creator>Kohno, Nobuoki</creator><creator>Okada, Morihito</creator><creator>Hattori, Noboru</creator><general>European Respiratory Society Journals Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8686-551X</orcidid></search><sort><creationdate>20180501</creationdate><title>Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-1c64e2e50c8f1c69d8a40ab2142e7c838ffbda709a4264ef45badc29c77bc1513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aminopeptidase</topic><topic>Angiogenesis</topic><topic>Antiangiogenic agents</topic><topic>CD13 antigen</topic><topic>Cisplatin</topic><topic>Medical prognosis</topic><topic>Mesothelioma</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Therapeutic applications</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Otsuki, Takahiko</creatorcontrib><creatorcontrib>Nakashima, Taku</creatorcontrib><creatorcontrib>Hamada, Hironobu</creatorcontrib><creatorcontrib>Takayama, Yusuke</creatorcontrib><creatorcontrib>Akita, Shin</creatorcontrib><creatorcontrib>Masuda, Takeshi</creatorcontrib><creatorcontrib>Horimasu, Yasushi</creatorcontrib><creatorcontrib>Miyamoto, Shintaro</creatorcontrib><creatorcontrib>Iwamoto, Hiroshi</creatorcontrib><creatorcontrib>Fujitaka, Kazunori</creatorcontrib><creatorcontrib>Miyata, Yoshihiro</creatorcontrib><creatorcontrib>Miyake, Masayuki</creatorcontrib><creatorcontrib>Kohno, Nobuoki</creatorcontrib><creatorcontrib>Okada, Morihito</creatorcontrib><creatorcontrib>Hattori, Noboru</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The European respiratory journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Otsuki, Takahiko</au><au>Nakashima, Taku</au><au>Hamada, Hironobu</au><au>Takayama, Yusuke</au><au>Akita, Shin</au><au>Masuda, Takeshi</au><au>Horimasu, Yasushi</au><au>Miyamoto, Shintaro</au><au>Iwamoto, Hiroshi</au><au>Fujitaka, Kazunori</au><au>Miyata, Yoshihiro</au><au>Miyake, Masayuki</au><au>Kohno, Nobuoki</au><au>Okada, Morihito</au><au>Hattori, Noboru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma</atitle><jtitle>The European respiratory journal</jtitle><addtitle>Eur Respir J</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>51</volume><issue>5</issue><spage>1701610</spage><epage>1701610</epage><pages>1701610-1701610</pages><issn>0903-1936</issn><eissn>1399-3003</eissn><abstract>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.</abstract><cop>England</cop><pub>European Respiratory Society Journals Ltd</pub><pmid>29519924</pmid><doi>10.1183/13993003.01610-2017</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-8686-551X</orcidid><oa>free_for_read</oa></addata></record> |
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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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