{"title":"Extracellular CD30 Regulates Brentuximab Vedotin-Induced Cell Death in an Adult T-Cell Leukemia Cell Line.","authors":"Keisuke Sato, Tomohiro Kozako, Akira Nakano, Naho Kato, Kentaro Ogata, Hidetoshi Kamimura, Hidenori Sasaki, Yasushi Takamatsu, Shigeki Takemoto, Shin-Ichiro Honda","doi":"10.1248/bpb.b24-00508","DOIUrl":null,"url":null,"abstract":"<p><p>Adult T-cell leukemia/lymphoma (ATL) is a malignant tumor of mature T lymphocytes induced by human T-cell leukemia virus 1, and it has a poor prognosis. Brentuximab vedotin (BV) is included in the treatment of CD30-positive ATL, but there are no predictive biomarkers for the treatment effects of BV. Serum soluble CD30 (sCD30) concentrations are increased in aggressive ATL at the time of diagnosis, but the effect of extracellular CD30 on BV-induced cell death in ATL is unknown. Similarly, a disintegrin and metalloproteinase 10 (ADAM10) and ADAM17 possess CD30 sheddase activity in anaplastic large cell lymphoma, but this activity is unclear in ATL. In this study, we showed that sCD30 concentrations were associated with BV activity in ATL-associated cell lines. Extracellular vesicles, such as exosomes containing CD30, also inhibited BV activity. Furthermore, knockdown of ADAM10/17 significantly reduced sCD30 concentrations and increased BV-induced cell death. These results suggest that ADAM10 and ADAM17 are involved in sCD30 production in ATL. Furthermore, endogenous extracellular CD30, such as sCD30 and CD30-positive extracellular vesicles shed by ADAM10/17, may be involved in BV-induced cell death. Taken together, our findings suggest that extracellular CD30 concentrations, including CD30 on extracellular vesicles, are a useful biomarker for BV therapy in ATL.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 9","pages":"1375-1383"},"PeriodicalIF":1.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological & pharmaceutical bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1248/bpb.b24-00508","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Adult T-cell leukemia/lymphoma (ATL) is a malignant tumor of mature T lymphocytes induced by human T-cell leukemia virus 1, and it has a poor prognosis. Brentuximab vedotin (BV) is included in the treatment of CD30-positive ATL, but there are no predictive biomarkers for the treatment effects of BV. Serum soluble CD30 (sCD30) concentrations are increased in aggressive ATL at the time of diagnosis, but the effect of extracellular CD30 on BV-induced cell death in ATL is unknown. Similarly, a disintegrin and metalloproteinase 10 (ADAM10) and ADAM17 possess CD30 sheddase activity in anaplastic large cell lymphoma, but this activity is unclear in ATL. In this study, we showed that sCD30 concentrations were associated with BV activity in ATL-associated cell lines. Extracellular vesicles, such as exosomes containing CD30, also inhibited BV activity. Furthermore, knockdown of ADAM10/17 significantly reduced sCD30 concentrations and increased BV-induced cell death. These results suggest that ADAM10 and ADAM17 are involved in sCD30 production in ATL. Furthermore, endogenous extracellular CD30, such as sCD30 and CD30-positive extracellular vesicles shed by ADAM10/17, may be involved in BV-induced cell death. Taken together, our findings suggest that extracellular CD30 concentrations, including CD30 on extracellular vesicles, are a useful biomarker for BV therapy in ATL.
期刊介绍:
Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012.
The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.