Novel treatment strategy targeting key regulators of cancer microenvironment formation
| Project/Area Number |
18H03004
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
清島 保 九州大学, 歯学研究院, 教授 (20264054)
中村 誠司 九州大学, 歯学研究院, 教授 (60189040)
松原 良太 九州大学, 歯学研究院, 共同研究員 (60615798)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 腫瘍微小環境 / 口腔扁平上皮癌 / ΔNp63 / 浸潤 / 転移 / 治療抵抗性 / 免疫監視機構 / 癌微小環境 / 口腔癌 / 頭頸部癌 / 浸潤・転移 / key regulator / がん / 微小環境 / がん微小環境 / 新しいがん治療 / がん転移 |
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| Outline of Final Research Achievements |
In this study, we focused on ΔNp63, a transcriptional factor, as a key-regulator which is involved in the formation of tumor-microenvironment in oral squamous cell carcinoma. Down-regulation of ΔNp63 induces epithelial-mesenchymal transition (EMT) and augments cell mobility through activation of Wnt5a-Ror2 signaling pathway. Furthermore, down-regulation of ΔNp63 also enhances resistance against chemoradiotherapy via IL-6 production and involved in the escape from immunosurveillance by inducing expression of PD-L1 and RCAS1. These results suggest that ΔNp63 plays a key role in the formation of tumor-microenvironment of OSCC.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、癌細胞は周囲の線維芽細胞、リンパ球、血管内皮細胞などの間質の細胞と密接に関わりながら、腫瘍微小環境（TAME）を構築し、浸潤・転移および治療抵抗性などの悪性形質獲得を獲得することが明らかとなっている。本研究により、口腔扁平上皮癌の浸潤先端部におけるTME構築にΔNp63が機能しており、癌の悪性形質の獲得に関与していることがことが明らかとなった。今後さらに研究を発展させ、ΔNp63の発現を制御する新規遺伝子を同定することが可能となれば、ΔNp63を標的とした口腔扁平上皮癌の新規治療法開発に寄与できるものと考えられる。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Prediction of nodal metastasis based on intraoral sonographic findings of the primary lesion in early-stage tongue cancer.2023
Author(s)
Kawano S, Hattori T, Mikami Y, Chikui T, Kawazu T, Sakamoto T, Maruse Y, Tanaka S, Hamada E, Hiwatashi M, Shiraishi Y, Oobu K, Kiyoshima T, Nakamura S.
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Journal Title
Int J Oral Maxillofac Surg.
Volume: 52
Issue: 5
Pages: 515-523
DOI
Related Report
Peer Reviewed
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