title: COX-2 Promotes Migration and Invasion by the Side Population of Cancer Stem Cell-Like Hepatocellular Carcinoma Cells.
abstract: Cancer stem cells (CSCs) are thought to be responsible for tumor relapse and metastasis due to their abilities to self-renew, differentiate, and give rise to new tumors. Cyclooxygenase-2 (COX-2) is highly expressed in several kinds of CSCs, and it helps promote stem cell renewal, proliferation, and radioresistance. Whether and how COX-2 contributes to CSC migration and invasion is unclear. In this study, COX-2 was overexpressed in the CSC-like side population (SP) of the human hepatocellular carcinoma (HCC) cell line HCCLM3. COX-2 overexpression significantly enhanced migration and invasion of SP cells, while reducing expression of metastasis-related proteins PDCD4 and PTEN. Treating SP cells with the selective COX-2 inhibitor celecoxib down-regulated COX-2 and caused a dose-dependent reduction in cell migration and invasion, which was associated with up-regulation of PDCD4 and PTEN. These results suggest that COX-2 exerts pro-metastatic effects on SP cells, and that these effects are mediated at least partly through regulation of PDCD4 and PTEN expression. These results further suggest that celecoxib may be a promising anti-metastatic agent to reduce migration and invasion by hepatic CSCs.
authors.affiliation: From the Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, P.R. China (ZG, H-JY, F-QY, Y-PQ, L-QL, B-DX); Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan, P.R. China (ZG); Department of General Surgery, The Second People's Hospital of The Second People's Hospital of Jingmen, Jingmen, P.R. China (J-HJ); Department of Ultrasound, Wuhan No. 1 Hospital, Wuhan, P.R. China (JZ); Medical Science Experimental Center, Guangxi Medical University, Nanning, P.R. China (Y-PZ, JS); Department of Immunology, School of Preclinical Medicine, Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, Nanning, P.R. China (R-RY).
authors.forename: Zhe
authors.initials: Z
authors.lastname: Guo
authors.forename: Jing-Hang
authors.initials: JH
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Yang
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Yang
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Qi
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Zhong
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.forename: Ri-Rong
authors.initials: RR
authors.lastname: Yang
authors.forename: Le-Qun
authors.initials: LQ
authors.lastname: Li
authors.forename: Bang-De
authors.initials: BD
authors.lastname: Xiang
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2