Yin Xiaowei, Lu Xuzhang, Xiuwen Zhang, Min Zhou, Xiao Rong, Mao Zhengdao, Zhang Qian
Department of Respiratory Medicine, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China.
Department of Hematology, Changzhou No. 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China.
Oncol Lett. 2017 May;13(5):3139-3143. doi: 10.3892/ol.2017.5800. Epub 2017 Mar 3.
It has been previously demonstrated that cytokine-induced killer (CIK) cells possess potent cytotoxicity against various cancer cells, including lung cancer cells. However, the mechanism by which CIK cells recognize lung cancer cells has not been understood. The interaction between killer cell lectin like receptor K1 (NKG2D) receptor and NKG2D ligands was demonstrated to serve an important role in target cell killing by natural killer cells. The present study investigated whether NKG2D receptor and NKG2D ligand interactions are involved in the CIK-directed killing of lung cancer cells. The expression of MICA and ULBP2 was detected in tumor and healthy tissue samples. The expression of MICA and ULBP2 in tumor tissue samples was higher compared with that in the healthy control tissue. The expression of NKG2D ligands was analyzed in A549 and Q56 cells through reverse transcription-quantitative polymerase chain reaction and flow cytometry. The results demonstrated that the lung cancer cell lines markedly expressed the NKG2D ligands. Furthermore, NKG2D ligand-expressing lung cancer cells were targeted by CIK cells, which was partially blocked by treating CIK cells with an antibody against NKG2D. The data of the current study has demonstrated that the NKG2D-NKG2D ligand interaction serves an essential role in mediating lung cancer cell killing by CIK cells.
先前已经证明,细胞因子诱导的杀伤(CIK)细胞对包括肺癌细胞在内的各种癌细胞具有强大的细胞毒性。然而,CIK细胞识别肺癌细胞的机制尚不清楚。杀伤细胞凝集素样受体K1(NKG2D)受体与NKG2D配体之间的相互作用被证明在自然杀伤细胞杀伤靶细胞中起重要作用。本研究调查了NKG2D受体与NKG2D配体的相互作用是否参与CIK细胞对肺癌细胞的杀伤作用。检测了肿瘤和健康组织样本中MICA和ULBP2的表达。与健康对照组织相比,肿瘤组织样本中MICA和ULBP2的表达更高。通过逆转录定量聚合酶链反应和流式细胞术分析了A549和Q56细胞中NKG2D配体的表达。结果表明,肺癌细胞系明显表达NKG2D配体。此外,表达NKG2D配体的肺癌细胞被CIK细胞靶向,用抗NKG2D抗体处理CIK细胞可部分阻断这种靶向作用。本研究的数据表明,NKG2D-NKG2D配体相互作用在介导CIK细胞杀伤肺癌细胞中起重要作用。