Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications.
Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications.
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表达NKG2D配体的宫颈癌细胞系能够对NKL细胞上的NKG2D受体调节，具有功能意义。
DOI：
10.1186/1471-2172-13-7
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发表时间：
2012-02-08
期刊：
影响因子：
3
通讯作者：
del Toro-Arreola S
中科院分区：
文献类型：
--
作者：
Jimenez-Perez MI;Jave-Suarez LF;Ortiz-Lazareno PC;Bravo-Cuellar A;Gonzalez-Ramella O;Aguilar-Lemarroy A;Hernandez-Flores G;Pereira-Suarez AL;Daneri-Navarro A;del Toro-Arreola S
宫颈癌是世界范围内第三大最常见的癌症，也是妇女癌症相关死亡的第四大原因。自然杀伤（NK）细胞在防御病毒、细胞内细菌和肿瘤中起重要作用。NKG 2D是NK细胞上的活化受体，识别MHC I类链相关分子，如云母/B和ULBP/RAET 1家族成员。已证明肿瘤源性可溶性NKG 2D配体可下调NK细胞上NKG 2D的表达。除了可溶性NKG 2D配体诱导的下调外，最近还描述了持续的细胞-细胞接触也可下调NKG 2D表达。本研究的目的是确定NKG 2D受体是否通过与宫颈癌细胞的细胞-细胞接触而下调，以及这种下调是否可能与NK细胞活性的变化相关。我们证明，NKL细胞上表达的NKG 2D通过与宫颈癌细胞系HeLa、SiHa和C33 A直接细胞接触而下调，但不与非致瘤性角质形成细胞（HaCaT）直接细胞接触。此外，这种下调具有功能性影响。我们发现NKG 2D配体在所有宫颈癌细胞系中表达，但配体分布模式在每个细胞系中不同。与NKL细胞或新鲜NK细胞共培养的宫颈癌细胞系诱导NKL细胞上的NKG 2D表达显著减少。此外，在与HeLa和SiHa细胞共培养后，NKL细胞对K562靶标的细胞毒活性受损，而与C33 A共培养增加了NKL细胞的细胞毒活性。我们的研究结果表明，宫颈癌细胞系中NKG 2D配体的差异表达可能与NKG 2D的下调以及与肿瘤细胞接触后NKL细胞的细胞毒活性变化有关。
Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.
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影响因子：
11.2
作者：
Ashiru O;Boutet P;Fernández-Messina L;Agüera-González S;Skepper JN;Valés-Gómez M;Reyburn HT
通讯作者：
Reyburn HT
影响因子：
3.7
作者：
Hedlund M;Nagaeva O;Kargl D;Baranov V;Mincheva-Nilsson L
通讯作者：
Mincheva-Nilsson L
影响因子：
100.3
作者：
Eagle, Robert A.;Trowsdale, John
通讯作者：
Trowsdale, John
DOI：
10.1073/pnas.0901173106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Li, Changlin;Houser, Brandy L.;Strominger, Jack L.
通讯作者：
Strominger, Jack L.
影响因子：
15.3
作者：
LITWIN, V;GUMPERZ, J;LANIER, LL
通讯作者：
LANIER, LL