| Project/Area Number |
18K09736
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Osaka Dental University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 口腔扁平上皮癌 / 癌幹細胞 / 幹細胞マーカー / c-Met / NF-κB / c-Myc / Snail |
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| Outline of Final Research Achievements |
In this study, We evaluated the immunohistochemical expression of NF-κB and ｃ-Met, which is also considered as an indicator of cancer stem cell (CSC), in oral squamous cell cartinoma(OSCC) clinical samples. Moreovere, analised the effects of NF-κB and ｃ-Met inhibition on migration and epithelial-mesenchymal transition (EMT) using western blot analysis and knockdown by NF-κB and ｃ-Met inhibitor in oral CSCs. Immunohistochemical staining of NF-κB andｃ-Met strongry expressed in the invasion front of the tumor cells. In OSCC cell lines, expression was observed in HSC3, HSC4 and KB, and in particular, phosphorylated NF-κB and ｃ-Met was clearly expressed in KB which showing stem cell-like property. Inhibition of NF-κB and ｃ-Met by inhibitor effectively inhibits the expression of genes involved in the EMT, and the migration of OSCCs.
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| Academic Significance and Societal Importance of the Research Achievements |
現在，臨床において口腔扁平上皮癌の分子レベルでの個体差を把握し治療法を決定することはなく，臨床的所見や経験に基づくところが大きい．そこで本研究では、NF-κBおよびc-Metの口腔扁平上皮癌における役割を明確にし，癌幹細胞マーカーとして治療法決定の際の指標とすることは，長年の目標である生存率の改善に大きく貢献するものと思われる．さらにNF-κB阻害剤やｃ-Met阻害剤により，NF-κBおよびc-Met発現を制御し，癌幹細胞性を抑制することで，新たな分子標的因子としての遺伝子治療へと応用できる可能性が示唆された．このことは学術的，社会的意義があり優れていると思われる．
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