title: Interleukin-6 from Ovarian Mesenchymal Stem Cells Promotes Proliferation, Sphere and Colony Formation and Tumorigenesis of an Ovarian Cancer Cell Line SKOV3.
abstract: The origin of the majority of epithelial ovarian cancers (EOC) is regarded as extraovarian, with the ovary being the secondary site. The aim of this study was to explore the possible role of ovarian mesenchymal stem cells (OvMSCs) and secreted IL-6 in the development of EOC. OvMSCs were derived from normal ovarian stroma. Cell surface markers and differentiation capability were determined. The effects of IL-6 and conditioned medium of OvMSCs on the malignant phenotype of SKOV3 ovarian cancer cells were tested, and the status of STAT3 and ERK phosphorylation was investigated. OvMSCs had similar surface marker profiles as bone marrow mesenchymal stem cells, i.e., CD44 (+), CD90 (+) and CD45 (-), and was readily inducible to osteogenic, adipogenic and chondrogenic differentiation. OvMSCs secreted an extremely high level (>2500 pg/ml) of IL-6. Treatment of SKOV3 cells with conditioned media from OvMSCs increased cell proliferation, tumor sphere formation and anchorage independent growth, and resulted in activation of STAT3 but not ERK. Coinjection of OvMSCs with SKOV3 cell enhanced tumorigenesis in NOD-SCID mice. All of these behaviors were blocked by IL-6 receptor blocking antibody administeredin vitroorin vivo. The OvMSCs alone injected into mice had no tumor growth after 3 months. By secreting high levels of IL-6, OvMSCs enhance the proliferation, sphere and colony formation and tumorigenesis of SKOV3 cells.
authors.affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital;; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: Dah-Ching
authors.initials: DC
authors.lastname: Ding
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan;; Department of Occupational Medicine, Buddhist Tzu Chi General Hospital.
authors.forename: Hwan-Wun
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital;; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan;; Cervical cancer prevention center, Buddhist Tzu Chi General Hospital.
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
keywords: IL-6, proliferation; SKOV3.; STAT3; tumorigenesis