title: Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Downregulates the Expression of Protumor Factors Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in a GM-CSF Receptor-Independent Manner in Cervical Cancer Cells.
abstract: Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner.
authors.affiliation: Department of Dermatovenerology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China ; Institute of Dermatovenerology, Wenzhou Medical University, Wenzhou 325000, China ; Jingmen First People's Hospital, Hubei 448000, China.
authors.forename: Nanyan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Dermatology, 105th Hospital of PLA, Hefei 230001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Rongying
authors.initials: R
authors.lastname: Ou
authors.affiliation: Department of Dermatovenerology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China ; Institute of Dermatovenerology, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2