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JBC:硒化合物可增强免疫系统抗癌症

JBC:硒化合物可增强免疫系统抗癌症

癌症如黑色素瘤,前列腺癌和某些类型的白血病通过过度激活天然免疫系统来削弱身体。现在哥本哈根大学的研究人员已经证实,天然存在的如大蒜,西兰花中的硒化合物会减慢免疫的过度反应。从长远来看,这可能会提高癌症治疗。该研究结果已发表在Journal of BioLogical Chemistry杂志上。

免疫系统主要目的是去除身体不正常的物质。因此,发生变化的细胞例如癌症细胞的前体细胞,通常被免疫系统识别清除。不幸的是,不同的癌症细胞中含有阻断免疫系统识别它们的机制,使癌症继续发展。

某些癌细胞过度表达液体形式的免疫刺激分子,过度刺激对免疫系统有负面影响。可以说,刺激分子过度激活免疫系统,并导致免疫系统崩溃。研究人员一直有兴趣阻断这种机制。现在,我们已经表明,某些硒化合物有效地阻断在癌症如恶性黑色素瘤,前列腺癌和某些类型的白血病中起重要作用的特殊免疫分子。

在这项研究中,研究人员着眼于所谓的NGK2D配体,其有8个变体,其中一个已引起了研究人员的注意。一旦癌症肆虐,可溶形式的NGK2D配体导致严重的问题。研究人员不断学习更多有关导致皮肤侵略性癌症,血液癌症和生殖器官癌症的机制。癌症如恶性黑色素瘤,前列腺癌和某些类型白血病的免疫刺激分子过表达显著削弱免疫系统。如果我们能够找到方法来减缓过度刺激,我们可以更好治疗肿瘤。

原文摘要:

The Selenium Metabolite Methylselenol Regulates the expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D*

Michael Hagemann-Jensen,et al.

For decades, selenium research has been focused on the identification of active metabolites, which are crucial for selenium chemoprevention of cancer. In this context, the metabolite methylselenol (CH3SeH) is known for its action to selectively kill transformed cells through mechanisms that include increased formation of reactive oxygen species, induction of DNA damage, triggering of apoptosis, and inhibition of angioGENEsis. Here we reveal that CH3SeH modulates the cell surface expression of NKG2D ligands. The expression of NKG2D ligands is induced by stress-associated pathways that occur early during malignant transformation and enable the recognition and elimination of tumors by activating the lymphocyte receptor NKG2D. CH3SeH regulated NKG2D ligands both on the transcriptional and the posttranscriptional levels. CH3SeH induced the transcription of MHC class I polypeptide-related sequence MICA/B and ULBP2 mRNA. However, the induction of cell surface expression was restricted to the ligands MICA/B. Remarkably, our studies showed that CH3SeH inhibited ULBP2 surface transport through inhibition of the autophagic transport pathway. Finally, we identified extracellular calcium as being essential for CH3SeH regulation of NKG2D ligands. A balanced cell surface expression of NKG2D ligands is considered to be an innate barrier against tumor development. Therefore, our work indicates that the application of selenium compounds that are metabolized to CH3SeH could improve NKG2D-based immune therapy.(doi:10.1074/jbc.M114.591537)

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