{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:16:14Z","timestamp":1760231774961,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["221S0001","S1311011","S1511008L"],"award-info":[{"award-number":["221S0001","S1311011","S1511008L"]}]},{"name":"Foundation of Strategic Research Projects in Private Universities of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)","award":["221S0001","S1311011","S1511008L"],"award-info":[{"award-number":["221S0001","S1311011","S1511008L"]}]},{"name":"Shizuoka Medical Research Center for Disaster of Juntendo University Shizuoka Hospital","award":["221S0001","S1311011","S1511008L"],"award-info":[{"award-number":["221S0001","S1311011","S1511008L"]}]},{"name":"The Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["221S0001","S1311011","S1511008L"],"award-info":[{"award-number":["221S0001","S1311011","S1511008L"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The expression of Renal Carcinoma (ERC)\/mesothelin is enhanced in a variety of cancers. ERC\/mesothelin contributes to cancer progression by modulating cell signals that regulate proliferation and apoptosis. Based on such biological insights, ERC\/mesothelin has become a molecular target for the treatment of mesothelioma, pancreatic cancer, and ovarian cancer. Recent studies revealed about 50\u201360% of colorectal adenocarcinomas also express ERC\/mesothelin. Therefore, colorectal cancer can also be a potential target of the treatment using an anti-ERC\/mesothelin antibody. We previously demonstrated an anti-tumor effect of anti-ERC antibody 22A31 against mesothelioma. In this study, we investigated the effect of 22A31 on a colorectal adenocarcinoma cell line, HCT116. The cells were xenografted into BALB\/c nu\/nu mice. All mice were randomly allocated to either an antibody treatment group with 22A31 or isotype-matched control IgG1\u03ba. We compared the volume of subsequent tumors, and tumors were pathologically assessed by immunohistochemistry. Tumors treated with 22A31 were significantly smaller than those treated with IgG1\u03ba and contained significantly fewer mitotic cells with Ki67 staining. We demonstrated that 22A31 exhibited a growth inhibitory property on HCT116. Our results implied that ERC\/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.<\/jats:p>","DOI":"10.3390\/cancers14092198","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T12:06:01Z","timestamp":1651147561000},"page":"2198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Inhibitory Effects of Anti-ERC\/Mesothelin Antibody 22A31 on Colorectal Adenocarcinoma Cells, within a Mouse Xenograft Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Gentaro","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"},{"name":"Department of Gastroenterology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Kajino","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"},{"name":"Department of Human Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Momose","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe 350-8550, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harumi","family":"Saeki","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Ohtsuji","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"},{"name":"Department of Human Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3558-7123","authenticated-orcid":false,"given":"Tomoyoshi","family":"Shibuya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Orimo","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihito","family":"Nagahara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumio","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okio","family":"Hino","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1073\/pnas.93.1.136","article-title":"Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers","volume":"93","author":"Chang","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_3","first-page":"3862","article-title":"Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: Identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE)","volume":"7","author":"Argani","year":"2001","journal-title":"Clin. Cancer. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/01.pai.00000141545.36485.d6","article-title":"Localization of mesothelin in epithelial ovarian cancer","volume":"13","author":"Hassan","year":"2005","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1158\/1078-0432.CCR-06-2161","article-title":"Mesothelin expression in human lung cancer","volume":"13","author":"Ho","year":"2007","journal-title":"Clin. Cancer. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ygyno.2006.10.063","article-title":"Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma","volume":"105","author":"Dainty","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1600-0609.2007.00928.x","article-title":"Mesothelin, a possible target for immunotherapy, is expressed in primary AML cells","volume":"79","author":"Steinbach","year":"2007","journal-title":"Eur. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.7150\/jca.1.141","article-title":"Mesothelin as a potential therapeutic target in human cholangiocarcinoma","volume":"1","author":"Yu","year":"2010","journal-title":"J. Cancer."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2174\/1871520611313020014","article-title":"The role of mesothelin in tumor progression and targeted therapy","volume":"13","author":"Tang","year":"2013","journal-title":"Anticancer. Agents. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1158\/1541-7786.MCR-08-0095","article-title":"Mesothelin-induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator transcription protein 3","volume":"6","author":"Bharadwaj","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Faust, J.R., Hamill, D., Kolb, E.A., Gopalakrishnapillai, A., and Barwe, S.P. (2022). Mesothelin: An immunotherapeutic target beyond solid tumors. Cancers, 14.","DOI":"10.3390\/cancers14061550"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9190","DOI":"10.1074\/jbc.M312372200","article-title":"Binding of ovarian cancer antigen CA125\/MUC16 to mesothelin mediates cell adhesion","volume":"279","author":"Rump","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1349-7006.2012.02214.x","article-title":"Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma","volume":"103","author":"Shimizu","year":"2012","journal-title":"Cancer. Sci."},{"key":"ref_14","first-page":"20","article-title":"Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin","volume":"7","author":"Hassan","year":"2007","journal-title":"Cancer Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1158\/1078-0432.CCR-10-2275","article-title":"Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers","volume":"16","author":"Hassan","year":"2010","journal-title":"Clin. Cancer. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Matsuzawa, F., Kamachi, H., Mizukami, T., Einama, T., Kawamata, F., Fujii, Y., Fukai, M., Kobayashi, N., Hatanaka, Y., and Taketomi, A. (2021). Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells. BMC Cancer, 21.","DOI":"10.1186\/s12885-020-07722-3"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40364-019-0169-8","article-title":"Mesothelin as a biomarker for targteted therapy","volume":"7","author":"Lv","year":"2019","journal-title":"Biomark Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1158\/1078-0432.CCR-09-0062","article-title":"Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P","volume":"15","author":"Kreitman","year":"2009","journal-title":"Clin. Cancer. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1158\/1535-7163.MCT-13-0926","article-title":"Anetumab ravtansine: A novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect","volume":"13","author":"Golfier","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1158\/1078-0432.CCR-21-1546","article-title":"Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia","volume":"27","author":"Le","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1038\/s41423-021-00749-x","article-title":"Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors","volume":"18","author":"Wang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1016\/j.ymthe.2019.07.015","article-title":"Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers","volume":"27","author":"Haas","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00535-013-0773-6","article-title":"C-ERC\/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma","volume":"49","author":"Kawamata","year":"2014","journal-title":"J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26744","DOI":"10.18632\/oncotarget.15814","article-title":"Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma","volume":"8","author":"Inaguma","year":"2017","journal-title":"Oncotarget"},{"key":"ref_25","first-page":"1741","article-title":"Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer","volume":"19","author":"Inoue","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1349-7006.2009.01463.x","article-title":"Antitumor activity of anti-C-ERC\/mesothelin monoclonal antibody in vivo","volume":"101","author":"Inami","year":"2010","journal-title":"Cancer. Sci."},{"key":"ref_27","first-page":"787","article-title":"Effects of mitomycin on human colon carcinoma cells","volume":"73","author":"Long","year":"1984","journal-title":"J. Natl. Cancer. Inst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jcb.240630505","article-title":"NCI-navy medical oncology branch cell line data base","volume":"63","author":"Phelps","year":"1996","journal-title":"J. Cell. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1440-1827.2009.02344.x","article-title":"Establishment of novel monoclonal antibody to human ERC\/mesothelin useful for study and diagnosis of ERC\/mesothelin-expressing cancers","volume":"59","author":"Ishikawa","year":"2009","journal-title":"Pathol. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"430","DOI":"10.7150\/ijbs.27050","article-title":"Polydatin increases radiosensitivity by inducing apoptosis of stem cells in colorectal cancer","volume":"15","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nri2744","article-title":"Monoclonal antibodies: Versatile platforms for cancer immunotherapy","volume":"10","author":"Weiner","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, K., Bodempudi, V., Liu, Z., Borrego-Diaz, E., Yamoutpoor, F., Meyer, A., Woo, R.A., Pan, W., Dudek, A.Z., and Olyaee, M.S. (2012). Inhibition of mesothelin as a novel strategy for targeting cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033214"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1126\/science.1719635","article-title":"GPI-anchored cell-surface molecules complexed to protein tyrosine kinases","volume":"254","author":"Stefanova","year":"1991","journal-title":"Science"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/9\/2198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:02:33Z","timestamp":1760137353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/9\/2198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["cancers14092198"],"URL":"https:\/\/doi.org\/10.3390\/cancers14092198","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,4,28]]}}}