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白细胞介素-6 促进鼻咽癌细胞系的迁移和侵袭,并上调 MMP-2 和 MMP-9 的表达。

Interleukin-6 promotes the migration and invasion of nasopharyngeal carcinoma cell lines and upregulates the expression of MMP-2 and MMP-9.

机构信息

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan 430030, P.R. China.

出版信息

Int J Oncol. 2014 May;44(5):1551-60. doi: 10.3892/ijo.2014.2323. Epub 2014 Mar 5.

DOI:10.3892/ijo.2014.2323
PMID:24603891
Abstract

Nasopharyngeal carcinoma (NPC) shows the highest invasive and metastatic features among head and neck cancers. Distant metastasis remains the predominant mode of treatment failure in NPC patients. The role of interleukin-6 (IL-6) in NPC progression is not fully understood. In this study, we explored whether IL-6 could promote the migration and invasion activity of NPC cell lines, as well as whether the effect of IL-6 on cell migration and invasion is mediated through regulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results revealed that IL-6 and its receptors are broadly expressed in various NPC cell lines including HNE1, HONE1, CNE1, CNE1-LMP1 and 5-8F. Exogenous IL-6 enhanced cell proliferation slightly, but promoted cell migration and invasion significantly in both HNE1 and CNE1-LMP1 cell lines. In addition, an elevation in the expression of MMP-2 and MMP-9 could be induced by IL-6 stimulation. On the contrary, combining treatment with monoclonal anti-human IL-6R antibody (anti-IL-6R mAb) resulted in decreased proliferation, migration and invasion capabilities of NPC cells. Anti-IL-6R mAb also inhibited the expression of MMP-2 and MMP-9 in IL-6-stimulated HNE1 and CNE1-LMP1 cells. In summary, our data suggested that IL-6 mainly promotes the cell migration and invasion of NPC cells. The effect of IL-6 on cell migration and invasion may be mediated through regulation of the expression of MMP-2 and MMP-9. Thus, IL-6 or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.

摘要

鼻咽癌(NPC)在头颈部癌症中具有最高的侵袭和转移特征。远处转移仍然是 NPC 患者治疗失败的主要模式。白细胞介素 6(IL-6)在 NPC 进展中的作用尚未完全阐明。在这项研究中,我们探讨了 IL-6 是否可以促进 NPC 细胞系的迁移和侵袭活性,以及 IL-6 对细胞迁移和侵袭的影响是否通过调节基质金属蛋白酶-2(MMP-2)和 MMP-9 的表达来介导。我们的结果表明,IL-6 及其受体广泛表达于各种 NPC 细胞系中,包括 HNE1、HONE1、CNE1、CNE1-LMP1 和 5-8F。外源性 IL-6 略微增强了细胞增殖,但明显促进了 HNE1 和 CNE1-LMP1 细胞系中的细胞迁移和侵袭。此外,IL-6 刺激可诱导 MMP-2 和 MMP-9 的表达升高。相反,与单克隆抗人 IL-6R 抗体(抗-IL-6R mAb)联合治疗可降低 NPC 细胞的增殖、迁移和侵袭能力。抗-IL-6R mAb 还抑制了 IL-6 刺激的 HNE1 和 CNE1-LMP1 细胞中 MMP-2 和 MMP-9 的表达。总之,我们的数据表明,IL-6 主要促进 NPC 细胞的迁移和侵袭。IL-6 对细胞迁移和侵袭的影响可能通过调节 MMP-2 和 MMP-9 的表达来介导。因此,IL-6 或其相关信号通路可能是预防和抑制 NPC 转移的有前途的靶点。

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