NKG2D ligands expression and NKG2D-Mediated cytotoxicity in human laryngeal squamous carcinoma cells

NKG2D ligands expression and NKG2D-Mediated cytotoxicity in human laryngeal squamous carcinoma cells
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DOI:
10.1111/j.1365-3083.2008.02086.x
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发表时间:
2008-05-01
影响因子:
3.7
通讯作者:
Zhang, D. L.
Zhang, D. L.
中科院分区:
医学4区
文献类型:
--
作者:
Chen, X. M.;Xu, X. Q.;Zhang, D. L.

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NKG 2D是一种由NK细胞和CD 8(+)T细胞表达的活化免疫受体。NKG 2D与其配体的结合对于先天性和过继性免疫都至关重要。虽然NKG 2D配体在某些肿瘤细胞上的过表达先前已得到证实,但对NKG 2D配体在人喉肿瘤细胞上的表达知之甚少。在这项研究中,我们首先验证了NKG 2D及其配体之间的相互作用是基于NK细胞的免疫应答对人喉鳞状细胞癌细胞Hep-2的关键。通过转染重组真核表达载体pEGFP-N1/NKG 2D及阻断NKG 2D,观察NKG 2D介导的细胞增殖效应。检测人喉癌细胞系Hep-2和新鲜肿瘤组织中NKG 2D配体、MHC I类相关链分子A(云母)和UL 16结合蛋白(ULBPs)的mRNA和蛋白表达。与声带息肉非肿瘤组织相比,云母和ULBP-3在人喉癌细胞系Hep-2和新鲜人喉癌组织中均强烈过表达。NKG 2D配体过表达对NK细胞介导的抗喉癌免疫应答的机制和影响需要进一步研究。
The NKG2D is an activating immunoreceptor expressed by NK cells and CD8(+) T cells. Engagement of NKG2D by its ligands is critical for both innate and adoptive immunity. While the overexpression of NKG2D ligands on certain tumour cells has previously been demonstrated, little is known about NKG2D ligand expression on human laryngeal tumour cells. In this study, we first verified that the interaction between NKG2D and its ligands was critical for NK cell-based immune response to human laryngeal squamous carcinoma cells Hep-2. This NKG2D-mediated effect was observed by transfecting the recombinant eukaryotic expression vector pEGFP-N1/NKG2D as well as the NKG2D blockade. The mRNA and protein expression of NKG2D ligands, MHC class I-related chain molecules A (MICA) and UL16-binding proteins (ULBPs), in human laryngeal carcinoma cell line Hep-2 and fresh tumour tissues were evaluated. Compared with non-tumour tissues of vocal cords polyps, MICA and ULBP-3 were strongly overexpressed on both the human laryngeal carcinoma cell line Hep-2 and fresh human laryngeal carcinoma tissues. The mechanism and impact of NKG2D ligands overexpression on NK cell-mediated anti-laryngeal cancer immune response would require further investigation.