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KAKEN_24592532seika.pdf
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Download
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:109.2 KB
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:Apr 11, 2016 |
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| Title |
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卵巣明細胞腺癌に高発現するHNF-1βによるがん微小環境構築機構の解明
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| Kana |
ランソウ メイサイボウセンガン ニ コウハツゲンスル HNF-1β ニ ヨル ガン ビショウ カンキョウ コウチク キコウ ノ カイメイ
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Ranso meisaibosengan ni kohatsugensuru HNF-1β ni yoru gan bisho kankyo kochiku kiko no kaimei
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Immunosuppressive roles of HNF-1beta in ovarian clear cell carcinoma (OCCC)
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藤田, 知信
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フジタ, トモノブ
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Fujita, Tomonobu
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慶應義塾大学・医学部・助教
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Research team head
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科研費研究者番号 : 20199334
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河上, 裕
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カワカミ, ユタカ
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Kawakami, Yutaka
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 50161287
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岩田, 卓
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イワタ, タカシ
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Iwata, Takashi
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 30296652
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青木, 大輔
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アオキ, ダイスケ
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Aoki, Daisuke
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 30167788
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2015
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科学研究費補助金研究成果報告書
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2014
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卵巣明細胞腺癌(OCCC)に高発現するhepatocyte nuclear factor-1β(HNF-1β)に着目し, がん微小環境における免疫抑制を検討した。HNF-1β高発現細胞株ではNF-kBやSTAT3の活性が高く, HNF-1β発現を抑制すると, NF-kBやSTAT3の活性が減弱しIL-6の産生も減少した。HNF-1βの発現抑制により共培養した樹状細胞が活性化され, そのT細胞刺激能も増強することがin vitroおよびin vivoにおいても示された。したがって, HNF-1βはOCCCのがん免疫抑制環境に関与するとともに, それを解除する標的分子となる可能性が示された。
Hepatocyte nuclear factor-1beta (HNF-1beta) is a transcription factor and is overexpressed in ovarian clear cell carcinoma (OCCC). Here, we investigated immunosuppressive roles of HNF-1beta in OCCC. IL-6 production and activation of NF-kB and STAT3 was associated with HNF-1beta accumulation in OCCC cell lines. Culture supernatants (CS) from HNF-1beta accumulated OCCC have activities to impair dendritic cells (DCs) maturation. These immunosuppressive CS activity was reduced by knocking down HNF-1beta, partly owing to down-regulation of IL-6. Murine splenic, lymphnode and tumor-infiltrating DCs obtained from nude mice implanted with HNF-1beta knocking down OCCC cells restored activity to activate T cell than did DCs from control OCCC cells. These results indicate that HNF-1beta in OCCC may be involved in the immunosuppression mediated by impaired DC, and is not only useful as the tumor marker but also attractive targets for restoring immunocompetence in patients with OCCC.
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研究種目 : 基盤研究(C)
研究期間 : 2012～2014
課題番号 : 24592532
研究分野 : がん免疫学
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