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KAKEN_26462623seika.pdf
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Download
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:Jul 30, 2019 |
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Total downloads since Jul 30, 2019 : 504
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頭頸部癌における低酸素誘導因子発現の転移への影響とその臨床応用に関する研究
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トウケイブガン ニ オケル テイサンソ ユウドウ インシ ハツゲン ノ テンイ エノ エイキョウ ト ソノ リンショウ オウヨウ ニ カンスル ケンキュウ
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Tokeibugan ni okeru teisanso yudo inshi hatsugen no teni eno eikyo to sono rinsho oyo ni kansuru kenkyu
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Analysis of HIF1-alpha expression for head and neck cancer metastasis
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小澤, 宏之
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オザワ, ヒロユキ
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Ozawa, Hiroyuki
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慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 30327621
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渡部, 佳弘
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ワタナベ, ヨシヒロ
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Watanabe, Yoshihiro
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慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 30445374
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佐藤, 陽一郎
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サトウ, ヨウイチロウ
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Sato, Yoichiro
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慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 4062440
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Chung, Christine
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Johns Hopkins University, Dept of Oncology, Head and Neck therapeutic program
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Research team member
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2017
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科学研究費補助金研究成果報告書
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2016
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| Abstract |
頭頸部癌症例のHIF1-α発現について検討を行った。早期舌癌25症例の免疫染色ではHIF1-αの核内発現と遅発性頸部転移との関係が示された。また経口的腫瘍切除の適応となった早期下咽頭癌症例においてリンパ節転移の有無とHIF1-α発現との間に相関を認めた。さらにHIF1-α阻害薬を用いて下流シグナルの変化をReal Time PCRで測定した。頭頸部癌細胞株にHIF1-α阻害薬を投与することにより, EMT関連遺伝子のなかではTWISTが, また癌幹細胞に関係するNANOGおよびOCT3/4遺伝子の発現が低下し, これらの遺伝子発現がHIF1-αにより制御され転移病巣形成に関与していることが示された。
The aim of the present study was to investigate the molecular targets of HIF1-α relevant to metastasis, and to find out an impact of HIF1-α to HNSCC metastasis by clinicopathological assays. In immunohistochemical study, the HIF-1α expression was higher in cancer cells than in normal cells of the adjacent normal mucosa. Univariate analysis revealed that high expression of HIF-1α was significantly correlated with T-classification (P=0.012), lymph node metastasis (P=0.002) and lymphatic invasion (P=0.03). HIF-1 inhibitor downregulated the expression of HIF-1α, twist, Oct3/4 and Nanog of head and neck cancer cells. These results suggest that HIF-1α plays a key role for the tumor progression of HNSCC through EMT and CSC property. From the present study, HIF-1α inhibition may have the possibility to suppress tumor metastasis, thus HIF-1α is attractive target for the treatment of HNSCC.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2014～2016
課題番号 : 26462623
研究分野 : 頭頸部外科
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