title: CCL18 from tumor-cells promotes epithelial ovarian cancer metastasis via mTOR signaling pathway.
abstract: CCL18 is a chemotactic cytokine involved in the pathogenesis and progression of various disorders, including cancer. Previously, our results showed high levels of CCL18 in the serum of epithelial ovarian carcinoma patients suggesting its potential as a circulating biomarker. In this study, we determined that CCL18 expression was up-regulated in ovarian carcinoma compared with adjacent tissue and was expressed in carcinoma cells in the tumor and not in normal ovarian epithelial cells by laser capture microdissection coupled with real-time RT-PCR. Moreover, correlation analysis showed that the CCL18 level was positively correlated with the metastasis of patients with ovarian cancer. Survival analysis also revealed that an increased level of CCL18 was associated with worse survival time in ovarian cancer patients. Over-expression of CCL18 led to enhanced migration and invasion of the Skov3 ovarian cancer cell line in vitro and in vivo. Finally, proteomics analysis demonstrated that CCL18-mediated ovarian cancer invasiveness was strongly correlated with the mTORC2 pathway. These findings suggest that the CCL18 chemokine has an important role in chemokine-mediated tumor metastasis, and may serve as a potential predictor for poor survival outcomes for ovarian cancer. © 2015 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Yu
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Mengdi
authors.initials: M
authors.lastname: Li
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Shi
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China.
authors.forename: Danrong
authors.initials: D
authors.lastname: Li
authors.affiliation: Research Department, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Gaungxi, China. lili@gxmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: chemokine (C-C motif) ligand 18; epithelial ovarian carcinoma; metastasis; signaling pathway