| Project/Area Number |
19K18973
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 角化 / 分化 / 周辺帯 / トランスグルタミナーゼ / 上皮内癌 |
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| Outline of Research at the Start |
口腔扁平上皮癌（OSCC）は角化傾向が極めて高く分化方向が明瞭なことが組織学的特徴である。高分化型OSCCは予後が良好で、角化がOSCCの生物学的特徴と関連している。高分化型OSCCには、非常に高い分化度を有し「超高分化型」ともいうべきOSCCがあり診断困難である。今回非角化上皮、錯角化上皮、上皮過形成症、高分化型OSCC、低分化型OSCCの5種のヒト口腔上皮から抽出したRNAをマイクロアレイ解析し、角化に深く関与する周辺帯の上流にある各マーカー遺伝子群を決定する。マーカー遺伝子の発現量比較から高分化型OSCCの診断に応用、遺伝子導入により低分化型OSCCから高分化型へ形質変化可能か検討する。
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| Outline of Final Research Achievements |
First, I identified loricrin as a gene that contributes to oral keratinization by performing RNA sequence analysis using normal keratinized epithelium and non-keratinized stratified squamous epithelium of the oral cavity. Next, by applying the three-dimensional culture method of the epidermis to the primary gingival epithelial cells, I created a keratinized multi-layered squamous epithelial model in which the epithelial cells are laminated and show differentiation over time. Furthermore, in this model, I thought that loricrin and its cross-linking enzyme, transglutaminase 3, were localized in the cells during the formation of the keratinized layer and contributed to keratinization. Finally, I used this three-dimensional culture to create a model of intraepithelial cancer showing a tendency to differentiate. Using these culture models, we established a method to compare normal and neoplastic differentiation / keratinization.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔の重層扁平上皮において、正常な分化・角化モデルと腫瘍性の分化・角化モデルを作成することができた。したがって、このモデルと網羅的な遺伝子解析を併用することにより、正常分化から腫瘍性分化への変化の観点から、口腔癌における腫瘍発生のメカニズムを遺伝学的に解明できる。
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