| Project/Area Number |
15K19175
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Laboratory medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SOEJIMA Yurie 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (60596964)
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| Research Collaborator |
FUKUSATO toshio
SAWABE motoji
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | インテグリンβ4 / インテグリンβ6 / 肝内胆管癌 / ラミニン5 / テネイシンC / TGF-β1 / α-SMA / 亜分類 / インテグリン / テネイシン / ラミニン / 混合型肝癌 / 細胞外基質 / stem cell features / 癌の浸潤 / 癌の進展 |
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| Outline of Final Research Achievements |
We immunohistochemically investigated α6β4 (β4) and αvβ6 (β6) integrin expressions in ICCs and evaluated their relationship with clinical and pathological parameters and ligand expression. β4 and β6 integrin levels were higher in non-peripheral central localization type ICC than in the peripheral localization type, in periductal-infiltrating or intraductal-growth types than in mass-forming type ICC, and in well-differentiated type than in poorly differentiated type ICC. High expression was related to bile duct invasion. In addition, β4 and β6 expressions were associated with laminin-5 and tenascin C. TGF-β1 and α-SMA-positive myofibroblasts were correlated with β6 expression. These results suggest that integrin expression is associated with subclassification and clinicopathological features of ICC through the coincident expression of their ligands and TGF-β1.
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| Academic Significance and Societal Importance of the Research Achievements |
肝内胆管癌、細胆管癌、混合型肝癌におけるインテグリンβ4, β6 の発現の特徴と関わる因子を調べ、これらの腫瘍の類似性、独立性、発生機序を検討した。特に肝内胆管癌では、インテグリンβ4, β6の発現がリガンドやTGF-β1の発現と関連して癌の亜分類および臨床病理学的因子と関連することを明らかにし、論文で報告した。
β4, β6 の発現は肝内胆管癌の小型末梢胆管から発生する癌で弱く、細胆管癌との類似性が示された。今後、肝内胆管癌においてインテグリンβ4, β6の発現を制御する因子を明らかにし、インテグリンβ4, β6を標的とし、かつ悪性度評価の指標とした治療応用への展開を目指す。
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