RRC ID 43929
Author Yanaihara N, Anglesio MS, Ochiai K, Hirata Y, Saito M, Nagata C, Iida Y, Takakura S, Yamada K, Tanaka T, Okamoto A.
Title Cytokine gene expression signature in ovarian clear cell carcinoma.
Journal Int J Oncol
Abstract Cytokine expression in a tumor microenvironment can impact both host defense against the tumor and tumor cell survival. In this study, we sought to clarify whether the cytokine gene expression profile could have clinical associations with ovarian cancer. We analyzed the expression of 16 cytokine genes (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-γ, TNF-α, IL-6, HLA-DRA, HLA-DPA1 and CSF1) in 50 ovarian carcinomas. Hierarchical clustering analysis of these tumors was carried out using Cluster software and differentially expressed genes were examined between clear cell carcinoma (CCC) and other subtypes. Following this examination we evaluated the biological significance of IL-6 knockdown in CCC. Unsupervised hierarchical clustering analysis of cytokine gene expression revealed two distinct clusters. The relationship between the two clusters and clinical parameters showed statistically significant differences in CCC compared to other histologies. CCC showed a dominant Th-2 cytokine expression pattern driven largely by IL-6 expression. Inhibition of IL-6 in CCC cells suppressed Stat3 signaling and rendered cells sensitive to cytotoxic agents. The unique cytokine expression pattern found in CCC may be involved in the pathogenesis of this subtype. In particular, high IL-6 expression appears likely to be driven by the tumor cells, fueling an autocrine pathway involving IL-6 expression and Stat3 activation and may influence survival when exposed to cytotoxic chemotherapy. Modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for CCC.
Volume 41(3)
Pages 1094-100
Published 2012-9-1
DOI 10.3892/ijo.2012.1533
PMID 22751940
MeSH Cell Line, Tumor Cytokines / biosynthesis Cytokines / genetics* Drug Resistance, Neoplasm Female Gene Expression Regulation, Neoplastic* Humans Interleukin-6 / biosynthesis Interleukin-6 / genetics* Multigene Family Ovarian Neoplasms / genetics* Ovarian Neoplasms / metabolism Ovary / metabolism Ovary / pathology RNA Interference RNA, Small Interfering STAT3 Transcription Factor / biosynthesis STAT3 Transcription Factor / metabolism Sarcoma, Clear Cell / genetics* Sarcoma, Clear Cell / metabolism Th2 Cells / metabolism* Transcriptome
IF 3.899
Times Cited 28
Human and Animal Cells