title: Cancer-associated fibroblasts enhance the migration ability of ovarian cancer cells by increasing EZH2 expression.
abstract: The tumor microenvironment is thought to affect malignant transformation and tumor progression. The histone methyltransferase, enhancer of zeste homologue 2 (EZH2), has recently been suggested to play a critical role in the tumorigenesis of several types of human cancer. The aim of this study was to investigate the effects of cancer-associated fibroblasts (CAFs) on the expression of EZH2 and the migration ability of ovarian cancer cells, in order to explore the link between the tumor microenvironment and epigenetic regulation. The ovarian cancer cell lines, A2780, SKOV3 and ES2, were indirectly co-cultured with primary ovarian CAFs or normal fibroblasts (NFs). The migration ability of the ovarian cancer cells was determined by Transwell migration assay. The expression levels of EZH2 were assessed by quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. The A2780-shEZH2 cells (A2780 cells transfected with shRNA targeting EZH2) were indirectly co-cultured with CAFs or NFs, and the changes in the expression levels of EZH2 and the migration ability of the cells were detected. The migration ability of the A2780, SKOV3 and ES2 cells co-cultured with CAFs was significantly enhanced (P<0.05) compared with the NF group and the cells cultured alone. The expression of EZH2 in the A2780, SKOV3 and ES2 cells was significantly increased following co-culture with CAFs (P<0.001) compared with the cells cultured alone but not those cultured with NFs. The migration ability of the A2780-shEZH2 cells was not significantly increased following co-culture with CAFs (P>0.05). Our data indicate that CAFs enhance the migration ability of ovarian cancer cells partly by increasing EZH2 expression.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Linjuan
authors.initials: L
authors.lastname: Xu
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Deng
authors.forename: Yinglian
authors.initials: Y
authors.lastname: Pan
authors.forename: Minggang
authors.initials: M
authors.lastname: Peng
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
authors.forename: Limian
authors.initials: L
authors.lastname: Song
authors.forename: Man
authors.initials: M
authors.lastname: Xiao
authors.forename: Zehua
authors.initials: Z
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2