Wang Lixin, Ma Ruixia, Kang Zhaopeng, Zhang Yupeng, Ding Hongcheng, Guo Weina, Gao Qing, Xu Min
Department of Otolaryngology head and neck surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Otolaryngology head and neck surgery, Affiliated People's Hospital of Hubei Medical University, Shiyan, China.
Department of Otolaryngology head and neck surgery, Hospital Affiliated to Ningxia Medical University, Yin chuan, China.
PLoS One. 2014 Sep 22;9(9):e108060. doi: 10.1371/journal.pone.0108060. eCollection 2014.
In carcinogenesis, inflammasomes may play contradictory roles through facilitating anti-tumor immunity or inducing oncogenic factors. Their function in cancer remains poorly characterized. In this study, we explored the effect of interleukin-17A (IL-17A) on the migration and invasion activity of nasopharyngeal carcinoma (NPC) cell lines and account for related mechanisms. Our results revealed that exogenous IL-17A promoted cell migration and invasion significantly in both NPC-039 and CNE-2Z cell lines. In addition, the expression of matrix metalloproteinase-2 (MMP-2)/-9 and Vimentin could be elevated by IL-17A stimulation; meanwhile the expression of E-cadherin was decreased. The results also show that IL-17A could activate the p38 signaling pathway in IL-17A-stimulated NPC-039 and CNE-2Z cell lines. Combining treatment with a p38 inhibitor (SB203580) resulted in decreased invasion capabilities of NPC-039 and CNE-2Z cell lines. SB203580 also inhibited the expression of MMP-2/-9 and increased the expression of E-cadherin in IL-17A-stimulated NPC-039 and CNE-2Z cell lines. IL-17A also could activate NF-κB in NPC-039 and CNE-2Z cell lines. In summary, our data show that IL-17A promote the cell migration and invasion of NPC cells. The effect of IL-17A on cell migration and invasion may be mediated via regulation of the expression of MMP-2/-9 and epithelial-mesenchymal transition (EMT) via p38-NF-κB signaling pathway. Thus, IL-17A or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.
在肿瘤发生过程中，炎性小体可能通过促进抗肿瘤免疫或诱导致癌因子发挥相互矛盾的作用。它们在癌症中的功能仍未得到充分表征。在本研究中，我们探讨了白细胞介素-17A（IL-17A）对鼻咽癌（NPC）细胞系迁移和侵袭活性的影响，并阐述相关机制。我们的结果显示，外源性IL-17A在NPC-039和CNE-2Z细胞系中均显著促进细胞迁移和侵袭。此外，IL-17A刺激可使基质金属蛋白酶-2（MMP-2）/-9和波形蛋白的表达升高；同时E-钙黏蛋白的表达降低。结果还表明，IL-17A可激活经IL-17A刺激的NPC-039和CNE-2Z细胞系中的p38信号通路。联合使用p38抑制剂（SB203580）导致NPC-039和CNE-2Z细胞系的侵袭能力下降。SB203580还抑制了经IL-17A刺激的NPC-039和CNE-2Z细胞系中MMP-2/-9的表达，并增加了E-钙黏蛋白的表达。IL-17A还可激活NPC-039和CNE-2Z细胞系中的NF-κB。总之，我们的数据表明IL-17A促进NPC细胞的迁移和侵袭。IL-17A对细胞迁移和侵袭的影响可能是通过p38-NF-κB信号通路调节MMP-(-9)的表达和上皮-间质转化（EMT）来介导的。因此，IL-17A或其相关信号通路可能是预防和抑制NPC转移的有前景的靶点。
