Research Papers:

Elevated autocrine chemokine ligand 18 expression promotes oral cancer cell growth and invasion via Akt activation

Xiao Jiang, Juan Wang, Xijuan Chen, Yun Hong, Tong Wu, Xiaobing Chen, Juan Xia _ and Bin Cheng

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Oncotarget. 2016; 7:16262-16272. https://doi.org/10.18632/oncotarget.7585

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Xiao Jiang1,2,*, Juan Wang1,*, Xijuan Chen1,*, Yun Hong1, Tong Wu1, Xiaobing Chen1, Juan Xia1, Bin Cheng1

1Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China

2Guangdong Provincial Stomatological Hospital, Guangzhou, Guangdong 510280, China

*These authors contributed equally to this work

Correspondence to:

Juan Xia, e-mail: xiajuan@mail.sysu.edu.cn

Bin Cheng, e-mail: chengbin@mail.sysu.edu.cn

Keywords: oral squamous cell carcinoma, chemokine (C-C motif) ligand 18 (CCL18), proliferation, invasion, Akt

Received: September 25, 2015     Accepted: February 05, 2016     Published: February 22, 2016


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.

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