Ezrin和Radixin对人胰腺导管腺癌KP-2细胞表面程序性死亡配体-1表达的差异调控

T. Kobori, Rina Doukuni, Honami Ishikawa, Yui Ito, Rie Okada, Chihiro Tanaka, Mayuka Tameishi, Y. Urashima, Takuya Ito, T. Obata
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引用次数: 7

摘要

免疫检查点阻断(ICB)疗法,如针对程序性死亡配体-1 (PD-L1)的免疫检查点抑制剂,在治疗胰腺导管腺癌(PDAC)患者中尚未成功。尽管PD-L1在各种类型的癌症中起着至关重要的作用,但PDAC细胞表面PD-L1表达的调控机制尚不清楚。因此,发现PD-L1细胞表面定位的潜在调节剂可能为改善PDAC患者的ICB治疗提供新的策略。在这里,我们研究了ezrin/radixin/moesin (ERM)家族支架蛋白在人PDAC细胞系KP-2细胞中PD-L1表面定位中的作用,该蛋白与肌动蛋白细胞骨架交联。我们的研究结果表明,PD-L1、ezrin和radixin表达丰富,但moesin不表达,并且它们在质膜上有共定位。有趣的是,免疫沉淀分析检测了PD-L1与ezrin和radixin的分子相互作用。此外,ezrin基因沉默可适度降低PD-L1 mRNA和细胞表面表达,而radixin基因沉默可在不改变mRNA水平的情况下显著降低PD-L1表面表达。因此,radixin和ezrin在KP-2细胞中差异调节PD-L1的细胞表面定位,突出了改善当前PDAC中ICB治疗的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ezrin and Radixin Differentially Modulate Cell Surface Expression of Programmed Death Ligand-1 in Human Pancreatic Ductal Adenocarcinoma KP-2 Cells
Immune checkpoint blockade (ICB) therapies, such as immune checkpoint inhibitors against programmed death ligand-1 (PD-L1), have not been successful in treating patients with pancreatic ductal adenocarcinoma (PDAC). Despite the critical role of PD-L1 in various types of cancers, the regulatory mechanism of PD-L1 expression on the cell surface of PDAC is poorly understood. Therefore, uncovering potential modulators of cell surface localisation of PD-L1 may provide a new strategy to improve ICB therapy in patients with PDAC. Here, we examined the role of ezrin/radixin/moesin (ERM) family scaffold proteins that crosslink transmembrane proteins with the actin cytoskeleton in the surface localisation of PD-L1 in KP-2 cells, a human PDAC cell line. Our results demonstrated the abundant protein expression of PD-L1, ezrin, and radixin, but not moesin, as well as their colocalisation in the plasma membrane. Interestingly, immunoprecipitation analysis detected the molecular interaction of PD-L1 with ezrin and radixin. Moreover, gene silencing of ezrin moderately decreased the mRNA and cell surface expression of PD-L1, while that of radixin greatly decreased the surface expression of PD-L1 without altering the mRNA levels. Thus, radixin and ezrin differentially modulate the cell surface localisation of PD-L1 in KP-2 cells, highlighting a potential therapeutic target to improve the current ICB therapy in PDAC.
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来源期刊
Immuno-Analyse & Biologie Specialisee
Immuno-Analyse & Biologie Specialisee 医学-医学实验技术
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