Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres
Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres
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DOI：
10.1016/j.canlet.2013.01.052
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发表时间：
2013-07-10
期刊：
影响因子：
9.7
通讯作者：
Mak, Nai-Ki
中科院分区：
文献类型：
--
作者：
Lo, Ming-Chu;Yip, Tak-Chun;Mak, Nai-Ki
巨噬细胞移动抑制因子（macrophagemigrationinhibitoryfactor，MIF）和趋化因子受体CXCL 8（CXCL 8，IL-8）在鼻咽癌（nasopharyngealcarcinoma，NPC）组织中呈强表达。然而，他们在NPC的成长中的作用尚未得到充分的研究。本研究旨在探讨MIF和CXCL 8对鼻咽癌肿瘤球生长的影响。在37对NPC患者的活检组织中证实了CXCL 8在肿瘤中的表达高于正常组织。在体外研究中，所有低分化鼻咽癌细胞系，包括EBV阳性的C666-1和EBV阴性的CNE-1、CNE-2、SUNE-1、HNE-1和HONE-1细胞，均被发现表达CXCL 8和MIF。因此，选择EBV阳性的C666-1细胞来检查MIF和CXCL 8在NPC肿瘤球生长中的作用。功能研究表明，CXCL 8特异性肽抑制剂可以抑制C666-1肿瘤球在营养不良或添加生长因子的培养条件下的生长。CXCR 2特异性抑制剂SB 225002或PI 3 K/AKT抑制剂LY 294002也可抑制肿瘤球的生长，表明内源性产生的CXCL 8在肿瘤球的生长中起自分泌作用。进一步的机制研究表明，MIF特异性小干扰RNA（siRNA）或NF-κ B B抑制剂parthenoprotein可抑制CXCL 8基因的表达，并抑制肿瘤球的生长。综上所述，本研究强调了MIF/CXCL 8/CXCR 2轴在NPC肿瘤球生长中的作用。化学干预这一信号通路可能有助于控制鼻咽癌的生长。(c)2013爱思唯尔爱尔兰有限公司版权所有。
Macrophage migration inhibitory factor (MIF) and CXCL8 (also named IL-8) are strongly expressed in the tissues of nasopharyngeal carcinoma (NPC). However, their role in the growth of NPC has not been fully examined. This study aims to evaluate the functions of MIF and CXCL8 on the growth of NPC tumor spheres. The elevated expression of CXCL8 in tumor over normal tissues was confirmed in 37 pairs of biopsies from NPC patients. In the in vitro study, all the poorly differentiated NPC cell lines, including the EBV-positive C666-1, and the EBV-negative CNE-1, CNE-2, SUNE-1, HNE-1 and HONE-1 cells, were found to express CXCL8 and MIF. Therefore, the EBV-positive C666-1 cell was selected to examine for the role of MIF and CXCL8 in the growth of the NPC tumor spheres. Functional study showed that the growth of C666-1 tumor spheres, under the nutrient poor or growth factor supplemented culture conditions, could be inhibited by the CXCL8 specific peptide inhibitor. The growth of the tumor spheres could also be reduced by the CXCR2 specific inhibitor SB225002 or the PI3K/AKT inhibitor LY294002, indicating that the endogenously produced CXCL8 plays an autocrine role in the growth of the tumor spheres. Further mechanistic studies revealed that the gene expression of CXCL8 could be reduced by the MIF specific small interfering RNA (siRNA) or NF-kappa B inhibitor parthenolide, and the growth of tumor spheres was also reduced after MIF siRNA transfection. Taken together, the present study highlights the role of MIF/CXCL8/CXCR2 axis in the growth of NPC tumor spheres. Chemotherapeutic interference of this signaling pathway may help to control the growth of the NPC tumor. (c) 2013 Elsevier Ireland Ltd. All rights reserved.