细胞外CD30调控Brentuximab vedotin诱导的成人t细胞白血病细胞系细胞死亡

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Keisuke Sato, Tomohiro Kozako, Akira Nakano, Naho Kato, Kentaro Ogata, Hidetoshi Kamimura, Hidenori Sasaki, Yasushi Takamatsu, Shigeki Takemoto, Shin-Ichiro Honda
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引用次数: 0

摘要

成人T细胞白血病/淋巴瘤(Adult T-cell leukemia/lymphoma, ATL)是由人T细胞白血病病毒1诱导的成熟T淋巴细胞恶性肿瘤,预后较差。Brentuximab vedotin (BV)被纳入cd30阳性ATL的治疗中,但目前还没有BV治疗效果的预测性生物标志物。在诊断时,侵袭性ATL患者血清可溶性CD30 (sCD30)浓度升高,但细胞外CD30对bv诱导的ATL细胞死亡的影响尚不清楚。同样,崩解素和金属蛋白酶10 (ADAM10)和ADAM17在间变性大细胞淋巴瘤中具有CD30脱落酶活性,但这种活性在ATL中尚不清楚。在这项研究中,我们发现sCD30浓度与atl相关细胞系的BV活性相关。细胞外囊泡,如含有CD30的外泌体,也能抑制BV活性。此外,敲低ADAM10/17显著降低sCD30浓度,增加bv诱导的细胞死亡。这些结果表明ADAM10和ADAM17参与了ATL中sCD30的产生。此外,内源性细胞外CD30,如由ADAM10/17脱落的sCD30和CD30阳性的细胞外囊泡,可能参与了bv诱导的细胞死亡。综上所述,我们的研究结果表明,细胞外CD30浓度,包括细胞外囊泡上的CD30,是ATL中BV治疗的有用生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extracellular CD30 Regulates Brentuximab Vedotin-Induced Cell Death in an Adult T-Cell Leukemia Cell Line.

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.

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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
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.
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