Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17
Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17
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DOI：
10.1038/cmi.2014.101
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发表时间：
2015-11-01
影响因子：
24.1
通讯作者：
Wang, Tingting
中科院分区：
文献类型：
--
作者：
Ren, Jing;Nie, Yunzhong;Wang, Tingting
雌激素参与促进肺癌细胞分裂和转移。MICA和MICB作为NKG2D的配体，NKG2D是一种在自然杀伤（NK）细胞上表达的重要免疫受体。然而，雌激素是否调控MICA/B表达并影响肿瘤免疫逃逸尚不清楚。在本研究中，我们测量了雌激素处理的非小细胞肺癌（NSCLC）细胞系中MICA、MICB和ADAM17的mRNA水平。流式细胞术检测MICA/B在ltp -a2和A549表面的表达。我们发现雌二醇可以上调肺腺癌细胞MICA/B的mRNA和分泌蛋白水平。雌二醇增强了ADAM17的表达，这与MICA/B的分泌有关。MICA/B的分泌下调了NK92细胞表面的NKG2D受体，损害了NK细胞的细胞毒活性。雌二醇增强了ADAM17的表达，这与MICA/B的分泌有关。此外，在NSCLC患者肿瘤组织中发现雌二醇浓度与MICA表达有显著相关性。因此，我们认为雌激素可以通过ADAM17调节MICA/B的表达和分泌，帮助肺癌细胞逃避nkg2d介导的免疫监视。
Estrogen is involved in promoting lung cancer cell division and metastasis. MICA and MICB function as ligands for NKG2D, an important immunoreceptor expressed on natural killer (NK) cells. However, whether estrogen regulates MICA/B expression and affects tumor immune escape remains unknown. In this study, we measured the mRNA levels of MICA, MICB and ADAM17 in non-small cell lung cancer (NSCLC) cell lines treated with estrogen. Surface expression of MICA/B on LTEP-a2 and A549 was detected using flow cytometry. We demonstrate that both mRNA and secretory protein levels of MICA/B in lung adenocarcinoma cell lines were upregulated by estradiol. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. This secretion of MICA/B downregulated the NKG2D receptor on the surface of NK92 cells and impaired the cytotoxic activity of NK cells. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. Furthermore, a significant correlation between the concentration of estradiol and the expression of MICA was found in tumor tissues of NSCLC patients. Therefore, we conclude that estrogen can regulate the expression and secretion of MICA/B through ADAM17, which helps lung cancer cells escape NKG2D-mediated immune surveillance.