| RRC ID |
36975
|
| 著者 |
Yanaihara N, Hirata Y, Yamaguchi N, Noguchi Y, Saito M, Nagata C, Takakura S, Yamada K, Okamoto A.
|
| タイトル |
Antitumor effects of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling pathway inhibition in clear cell carcinoma of the ovary.
|
| ジャーナル |
Mol Carcinog
|
| Abstract |
Among epithelial ovarian cancers, clear cell carcinoma of the ovary (CCC) has unique clinical and molecular characteristics that include chemoresistance resulting in poor prognosis. It was shown that CCC recently was characterized by specific upregulation of the IL-6/IL-6R-signal transducer and activator of transcription 3 (Stat3) signaling pathway. In this study, we aim to clarify whether IL-6/IL-6R mediated signaling pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases collected from primary surgical specimens were evaluated by the immunohistochemical analysis for IL-6R and phosphorylated Stat3 (pStat3), and we found that high IL-6R expression correlated with poor patient survival both by the univariate and multivariate analyses, suggesting that IL-6/IL-6R signaling pathway could be implicated in the progression of CCC. We further investigated the effects of IL-6/IL-6R mediated signaling pathway inhibition either by IL-6R small interfering RNA (siRNA) approach or humanized anti-human IL-6R antibody (tocilizumab) in CCC. Inhibition of endogenous IL-6R including tocilizumab in CCC cells did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL-6/IL-6R signaling pathway could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL-6R mediated signaling pathway could be a promising therapeutic strategy for CCC.
|
| 巻・号 |
55(5)
|
| ページ |
832-41
|
| 公開日 |
2016-5-1
|
| DOI |
10.1002/mc.22325
|
| PMID |
25856562
|
| MeSH |
Adenocarcinoma, Clear Cell / genetics
Adenocarcinoma, Clear Cell / metabolism
Adenocarcinoma, Clear Cell / pathology*
Antibodies, Monoclonal, Humanized / pharmacology*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Interleukin-6 / genetics
Interleukin-6 / metabolism*
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology*
Phosphorylation / drug effects
Prognosis
Receptors, Interleukin-6 / genetics
Receptors, Interleukin-6 / metabolism*
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects
|
| IF |
3.825
|
| 引用数 |
22
|
|
WOS 分野
|
ONCOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
JHOC-5(RCB1520)
JHOC-7(RCB1688)
JHOC-8(RCB1723)
JHOC-9(RCB2226) |
