RRC ID 35671
Author Kawano M, Mabuchi S, Matsumoto Y, Sasano T, Takahashi R, Kuroda H, Kozasa K, Hashimoto K, Isobe A, Sawada K, Hamasaki T, Morii E, Kimura T.
Title The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer.
Journal Sci Rep
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.
Volume 5
Pages 18217
Published 2015-12-15
DOI 10.1038/srep18217
PII srep18217
PMID 26666576
PMC PMC4678366
MeSH Animals Antineoplastic Combined Chemotherapy Protocols / therapeutic use Cell Line, Tumor Cell Proliferation Disease Models, Animal Drug Resistance, Neoplasm* / genetics Female Gene Expression Regulation, Neoplastic* Granulocyte Colony-Stimulating Factor / genetics* Mice Myeloid Cells / immunology* Myeloid Cells / metabolism* Platinum / administration & dosage Prognosis Uterine Cervical Neoplasms / drug therapy Uterine Cervical Neoplasms / genetics* Uterine Cervical Neoplasms / immunology* Uterine Cervical Neoplasms / mortality Uterine Cervical Neoplasms / pathology
IF 4.122
Times Cited 7
DNA material pCAmGCSF (RDB01522)