title: Expression of the miR200 family of microRNAs in mesothelial cells suppresses the dissemination of ovarian cancer cells.
abstract: The TGFβ-mediated alteration of the tumor microenvironment plays a crucial role in tumor progression. Mesothelial cells are the primary components of the tumor microenvironment for ovarian cancer cells; however, the exact role of TGFβ-stimulated mesothelial cells in ovarian cancer progression remains uncertain. In this report, we examined the effects of TGFβ-treated mesothelial cells on ovarian cancer progression. We show that TGFβ-stimulated human primary mesothelial cells (HPMC) are able to promote cancer cell attachment and proliferation and the activation of the promoter activities of MMP-2 and MMP-9, which are metalloproteinases necessary for tumor invasion. Expression of the miR200 family was downregulated in HPMCs by TGFβ stimulation, and restoration of the expression of miR200 family members in HPMCs suppressed cancer cell attachment and proliferation. Downregulation of the miR200 family by TGFβ induced fibronectin 1 production, which promoted cancer cell attachment to HPMCs. Finally, we demonstrated that the delivery of the miR200s to mesothelial cells in mice inhibited ovarian cancer cell implantation and dissemination. Our results suggest that alteration of the tumor microenvironment by the miR200 family could be a novel therapeutic strategy for ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, and.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Obstetrics and Gynecology, and kajiyama@med.nagoya-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.affiliation: Department of Obstetrics and Gynecology, and.
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Obstetrics and Gynecology, and.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Obstetrics and Gynecology, and.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.affiliation: Division of Cancer Biology, Nagoya University Graduate School of Medicine, Showa, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C067625:FN1 protein, human; D005353:Fibronectins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta