Roles of CXCL8 in squamous cell carcinoma proliferation and migration
Roles of CXCL8 in squamous cell carcinoma proliferation and migration
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DOI：
10.1016/j.oraloncology.2007.12.002
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Yeudall, W. Andrew
中科院分区：
文献类型：
--
作者：
Christofakis, Emil P.;Miyazaki, Hiroshi;Yeudall, W. Andrew
我们实验室之前的工作已经证明了趋化因子在头颈癌中的过表达，以及在临床前靶向CXCL5用于肿瘤治疗的实用性。模型。在本研究中，我们研究了一种相关趋化因子CXCL8对与肿瘤进展相关的细胞特性（即细胞生长和运动）的贡献。CXCL8的表达在多个鳞状癌细胞中均可检测到，表明其可能在发病机制中起重要作用。通过细胞计数和MTT检测发现，在内源性CXCL8水平较低的HN4原发肿瘤细胞中，过表达CXCL8可促进细胞生长。相反，在同步转移的HN12细胞中，rnai介导的CXCL8表达下调导致增殖减少，该细胞表达高水平的趋化因子。同样，过表达CXCL8可增强HN4细胞的迁移，而抑制CXCL8可通过基底膜替代物抑制HN12细胞的迁移和侵袭。综上所述，这些发现支持了CXCL8影响肿瘤进展的多个过程的假设，并确定了CXCL8作为一个潜在的治疗靶点，类似于CXCL5。(C) 2007 Elsevier Ltd.版权所有。
Previous work from our laboratory has demonstrated overexpression of chemokines in head and neck cancer, and the utitity of targeting CXCL5 for tumor therapy in a preclinical. model. In the present study, we investigated the contribution of a related chemokine, CXCL8, to cellular properties associated with tumor progression, namely cell growth and motility. Expression of CXCL8 was detectable in multiple squamous carcinoma cell tines, indicating a possible rote in pathogenesis. Overexpression of CXCL8 in HN4 primary tumor cells with low endogenous CXCL8 levels was found to increase cell growth, as judged by cell counting and MTT assays. Conversely, RNAi-mediated knockdown of CXCL8 expression in HN12 cells, derived from a synchronous metastasis and which express high levels of this chemokine, resulted in a decrease in proliferation. Similarly, overexpression of CXCL8 enhanced migration of HN4 cells, while suppression of CXCL8 inhibited HN12 cell migration and invasion through a basement membrane substitute. Taken together, these findings support the hypothesis that CXCL8 affects multiple processes involved in tumor progression and identify CXCL8 as a potential therapeutic target, similar to CXCL5. (C) 2007 Elsevier Ltd. All rights reserved.