title: Interleukin 6 receptor is an independent prognostic factor and a potential therapeutic target of ovarian cancer.
abstract: Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment.
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Aki
authors: A
authors: Isobe
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Kenjiro
authors: K
authors: Sawada
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yasuto
authors: Y
authors: Kinose
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; Department of Obstetrics and Gynecology, JCHO Osaka Hospital, Osaka, Japan.
authors: Chifumi
authors: C
authors: Ohyagi-Hara
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Erika
authors: E
authors: Nakatsuka
authors: Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Hiroshi
authors: H
authors: Makino
authors: Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Tomonori
authors: T
authors: Ogura
authors: Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Tomoko
authors: T
authors: Mizuno
authors: Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Noriko
authors: N
authors: Suzuki
authors: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Eiichi
authors: E
authors: Morii
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Koji
authors: K
authors: Nakamura
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Ikuko
authors: I
authors: Sawada
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Aska
authors: A
authors: Toda
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Kae
authors: K
authors: Hashimoto
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Seiji
authors: S
authors: Mabuchi
authors: Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Tsuyoshi
authors: T
authors: Ohta
authors: Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Ken-ichirou
authors: K
authors: Morishige
authors: Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Hirohisa
authors: H
authors: Kurachi
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Tadashi
authors: T
authors: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D039481:CD11b Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D019899:Paracrine Communication; D010641:Phenotype; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D039481:CD11b Antigen; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D019947:Receptors, Interleukin-6; D042461:Vascular Endothelial Growth Factor A