title: The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer.
abstract: Granulocyte-colony stimulating factor (G-CSF) producing malignant tumor has been reported to occur in various organs, and has been associated with poor clinical outcome. The aim of this study is to investigate the significance of tumor G-CSF expression in the chemosensitivity of uterine cervical cancer. The clinical data of recurrent or advanced cervical cancer patients who were treated with platinum-based chemotherapy were analyzed. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were employed to examine the mechanisms responsible for the development of chemoresistance in G-CSF-producing cervical cancer, focusing on myeloid-derived suppressor cells (MDSC). As a result, the tumor G-CSF expression was significantly associated with increased MDSC frequencies and compromised survival. In vitro and in vivo experiments demonstrated that the increased MDSC induced by tumor-derived G-CSF is involved in the development of chemoresistance. The depletion of MDSC via splenectomy or the administration of anti-Gr-1 antibody sensitized G-CSF-producing cervical cancer to cisplatin. In conclusion, tumor G-CSF expression is an indicator of an extremely poor prognosis in cervical cancer patients that are treated with chemotherapy. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy as a treatment for G-CSF-producing cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Mahiru
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mabuchi
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sasano
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kuroda
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kozasa
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Isobe
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Sawada
authors.affiliation: Department of Biomedical Statistics Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: Department of Molecular Pathology; Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Obstetrics and Gynecology Osaka University Graduate School of Medicine; 2-2 Yamadaoka; Suita; Osaka; 565-0871; Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D010984:Platinum / Q000008:administration & dosage; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D010984:Platinum