title: Elevated autocrine chemokine ligand 18 expression promotes oral cancer cell growth and invasion via Akt activation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xia
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D019742:Chemokines, CC / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; chemokine (C-C motif) ligand 18 (CCL18); invasion; oral squamous cell carcinoma; proliferation