{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:51:34Z","timestamp":1775267494782,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI\/24570142, 25290047, 26830087"],"award-info":[{"award-number":["KAKENHI\/24570142, 25290047, 26830087"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,3]]},"abstract":"Carbonic anhydrase IX<\/jats:styled-content> (CA<\/jats:styled-content>9) is a membrane\u2010associated carbonic anhydrase that regulates cellular pH<\/jats:styled-content>, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA<\/jats:styled-content>9 in the tumorigenicity of cells derived from human adult T\u2010cell leukemia\/lymphoma (ATL<\/jats:styled-content>). We previously established the highly tumorigenic ST<\/jats:styled-content>1\u2010N6 subline from the ATL<\/jats:styled-content>\u2010derived ST<\/jats:styled-content>1 cell line by serial xenotransplantation in NOG<\/jats:styled-content> mice. In the present study, we first show that CA<\/jats:styled-content>9 expression is strongly enhanced in ST<\/jats:styled-content>1\u2010N6 cells. We then sorted ST<\/jats:styled-content>1 cells by high or low CA<\/jats:styled-content>9 expression and established ST<\/jats:styled-content>1\u2010CA<\/jats:styled-content>9high<\/jats:sup> and ST<\/jats:styled-content>1\u2010CA<\/jats:styled-content>9low<\/jats:sup> sublines. ST<\/jats:styled-content>1\u2010CA<\/jats:styled-content>9high<\/jats:sup> cells, like ST<\/jats:styled-content>1\u2010N6 cells, were more strongly tumorigenic than ST<\/jats:styled-content>1\u2010CA<\/jats:styled-content>9low<\/jats:sup> or parental ST<\/jats:styled-content>1 cells when injected into NOG<\/jats:styled-content> mice. Knockdown of CA<\/jats:styled-content>9 with shRNA<\/jats:styled-content>s suppressed the ability of ST<\/jats:styled-content>1\u2010CA<\/jats:styled-content>9high<\/jats:sup> cells to initiate tumors, and the tumorigenicity of ST<\/jats:styled-content>1 cells was significantly enhanced by introducing wild\u2010type CA<\/jats:styled-content>9 or a CA<\/jats:styled-content>9 mutant with deletion of an intracytoplasmic domain. However, a CA<\/jats:styled-content>9 with point mutations in the catalytic site did not increase the tumorigenicity of ST<\/jats:styled-content>1 cells. Furthermore, we detected a small population of CA<\/jats:styled-content>9+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> cells in lymph nodes of ATL<\/jats:styled-content> patients. These findings suggest that CA<\/jats:styled-content>9, and particularly its carbonic anhydrase activity, promotes the tumorigenicity of ATL<\/jats:styled-content>\u2010derived cells and may be involved in malignant development of lymphoma\u2010type ATL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.13163","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T15:51:29Z","timestamp":1484149889000},"page":"435-443","source":"Crossref","is-referenced-by-count":11,"title":["Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T\u2010cell leukemia\u2010derived cells"],"prefix":"10.1111","volume":"108","author":[{"given":"Kentaro","family":"Nasu","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Oncology Miyagi Cancer Center Research Institute Natori Japan"},{"name":"Department of Hematology and Rheumatology Tohoku University Graduate School of Medicine Sendai 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Stem Cell Miyagi Cancer Center Research Institute Natori Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cancer Science Tohoku University Graduate School of Medicine Sendai Japan"},{"name":"Division of Cancer Biology and Therapeutics Miyagi Cancer Center Research Institute Natori Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuetsu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Immunology Graduate School of Medicine University of the Ryukyus Okinawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Laboratory of Hemato\u2010Immunology Faculty of Medicine School of Health Sciences University of the Ryukyus Okinawa 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