Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid
Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid
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DOI：
10.1080/2162402x.2016.1259049
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Seliger, Barbara
中科院分区：
文献类型：
--
作者：
Lennicke, Claudia;Rahn, Jette;Seliger, Barbara
人体必需的微量元素硒（Se）在癌症的预防和治疗中可能发挥作用。其代谢产物甲基硒醇能够通过不同的机制杀死细胞，包括诱导活性氧、DNA损伤和凋亡。由于甲基硒醇通过调节NKG 2D配体的表达来影响先天性免疫应答，因此本研究的目的是确定产生甲基硒醇的化合物甲基硒酸（MSA）是否影响MHC I类表面抗原的表达和生长特性，从而逆转免疫逃逸。但硒代蛋氨酸和亚硒酸盐不能导致MHC I类细胞表面抗原的剂量依赖性上调。这是由于抗原加工机制（APM）和干扰素（IFN）信号通路的一些主要成分的转录上调，并伴随着MSA存在下B16 F10黑色素瘤细胞迁移减少。未处理和MSA处理的黑色素瘤细胞的比较性“ome”分析将抗氧化反应系统与MHC I类抗原加工联系起来。由于MSA处理增强了MHC I类表面表达也在不同的人肿瘤细胞系，MSA可能会影响各种肿瘤细胞的恶性表型，通过恢复MHC I类APM组分的表达，由于改变的氧化还原状态，并通过部分模拟IFN-γ信号转导，从而提供了一种新的机制，甲基硒醇产生硒化合物的化疗潜力。
The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape.Treatment of B16F10 melanoma cells expressing low basal MHC class I surface antigens with dimethyldiselenide (DMDSe) and MSA, but not with selenomethionine and selenite resulted in a dose-dependent upregulation of MHC class I cell surface antigens. This was due to a transcriptional upregulation of some major components of the antigen processing machinery (APM) and the interferon (IFN) signaling pathway and accompanied by a reduced migration of B16F10 melanoma cells in the presence of MSA. Comparative "ome"-based profilings of untreated and MSA-treated melanoma cells linked the anti-oxidative response system with MHC class I antigen processing. Since MSA treatment enhanced MHC class I surface expression also on different human tumors cell lines, MSA might affect the malignant phenotype of various tumor cells by restoring MHC class I APM component expression due to an altered redox status and by partially mimicking IFN-gamma signaling thereby providing a novel mechanism for the chemotherapeutic potential of methylselenol generating Se compounds.