Jiang Xiao, Wang Juan, Chen Xijuan, Hong Yun, Wu Tong, Chen Xiaobing, Xia Juan, Cheng Bin
Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
Guangdong Provincial Stomatological Hospital, Guangzhou, Guangdong 510280, China.
Oncotarget. 2016 Mar 29;7(13):16262-72. doi: 10.18632/oncotarget.7585.
Chemokine (C-C motif) ligand 18 (CCL18) has been implicated in the pathogenesis and progression of various cancers; however, in oral squamous cell carcinoma (OSCC), the role of CCL18 is unknown. In this study, we found that CCL18 was overexpressed in primary OSCC tissues and was associated with an advanced clinical stage. CCL18 was found in both the cytoplasm and cell membrane of OSCC cells and was predominantly produced by cancer epithelial cells, as opposed to tumor-infiltrating macrophages. In vitro studies indicated that the effects of endogenous CCL18 on OSCC cell growth, migration, and invasion could be blocked by treatment with a neutralizing anti-CCL18 antibody or CCL18 knockdown, while exogenous recombinant CCL18 (rCCL18) rescued those effects. Akt was activated in rCCL18-treated OSCC cells, while LY294002, a pan-PI3K inhibitor, abolished both endogenous and exogenous CCL18-induced OSCC cell invasion. In vivo, LY294002 treatment attenuated rCCL18-induced OSCC cell growth. Our results indicate that CCL18 acts in an autocrine manner via Akt activation to stimulate OSCC cell growth and invasion during OSCC progression. They also provide a potential therapeutic target for the treatment of oral cancer.
趋化因子（C-C基序）配体18（CCL18）与多种癌症的发病机制和进展有关；然而，在口腔鳞状细胞癌（OSCC）中，CCL18的作用尚不清楚。在本研究中，我们发现CCL18在原发性OSCC组织中过表达，并与晚期临床分期相关。CCL18在OSCC细胞的细胞质和细胞膜中均有发现，主要由癌上皮细胞产生，而非肿瘤浸润巨噬细胞。体外研究表明，用中和抗CCL18抗体处理或敲低CCL18可阻断内源性CCL18对OSCC细胞生长、迁移和侵袭的影响，而外源性重组CCL18（rCCL18）可恢复这些影响。在rCCL18处理的OSCC细胞中Akt被激活，而泛PI3K抑制剂LY294002可消除内源性和外源性CCL18诱导的OSCC细胞侵袭。在体内，LY294002处理可减弱rCCL18诱导的OSCC细胞生长。我们的结果表明，CCL18在OSCC进展过程中通过激活Akt以自分泌方式刺激OSCC细胞生长和侵袭。它们还为口腔癌的治疗提供了一个潜在的治疗靶点。
