Elevated autocrine chemokine ligand 18 expression promotes oral cancer cell growth and invasion via Akt activation.
Elevated autocrine chemokine ligand 18 expression promotes oral cancer cell growth and invasion via Akt activation.
复制标题
自分泌趋化因子配体 18 表达升高通过 Akt 激活促进口腔癌细胞生长和侵袭
DOI：
10.18632/oncotarget.7585
复制
发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Cheng B
中科院分区：
文献类型：
--
作者：
Jiang X;Wang J;Chen X;Hong Y;Wu T;Chen X;Xia J;Cheng B
趋化因子（C-C基序）配体18（CCL 18）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，CCL 18的作用尚不清楚。在这项研究中，我们发现CCL 18在原发性OSCC组织中过表达，并且与晚期临床分期相关。CCL 18在OSCC细胞的细胞质和细胞膜中均被发现，并且主要由癌上皮细胞产生，而不是肿瘤浸润性巨噬细胞。体外研究表明，内源性CCL 18对OSCC细胞生长、迁移和侵袭的作用可以通过中和性抗CCL 18抗体或CCL 18敲低来阻断，而外源性重组CCL 18（rCCL 18）挽救了这些作用。Akt在rCCL 18处理的OSCC细胞中被激活，而LY 294002，一种pan-PI 3 K抑制剂，消除内源性和外源性CCL 18诱导的OSCC细胞侵袭。在体内，LY 294002处理减弱rCCL 18诱导的OSCC细胞生长。我们的研究结果表明，CCL 18的行为在自分泌的方式通过Akt激活，以刺激OSCC细胞的生长和侵袭在OSCC的进展。它们还为口腔癌的治疗提供了潜在的治疗靶点。
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.