Development of gene therapy for oral cancer using Sendai virus vector with alpha2-antiplasmin gene
| Project/Area Number |
17K11875
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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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| Research Field |
Surgical dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
hamana tomoaki 広島大学, 医系科学研究科(歯), 助教 (40397922)
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| Co-Investigator(Kenkyū-buntansha) |
岡本 哲治 広島大学, 医系科学研究科(歯), 教授 (00169153)
林堂 安貴 広島大学, 病院(歯), 講師 (70243251)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | α2-アンチプラスミン / プラスミン / E-カドヘリン / センダイウイルスベクター / 口腔癌遺伝子治療 |
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| Outline of Final Research Achievements |
It was indicated that β-catenin which bind to cytodomain of E-cadherin translocated from the plasma membrane to the nucleus by treatment of squamous cell carcinoma cells with plasminogen. Furthermore, upregulation of cyclin D1 was also observed. Therefore, it was suggested that it might promote cell proliferation by the translocating β-catenin into the nucleus associated with the cleavage of E-cadherin by plasmin.
These findings suggest that the suppression of the plasminogen activator/plasmin system by alpha2-antiplasmin might reduce the proliferation of OSCC cells. Therefore, it could be expected the development of gene therapy for invasiveness and metastasis of OSCC cells with induction of alpha2- antiplasmin into OSCC tissue.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでにプラスミンが，E-カドヘリンを切断することで，口腔扁平上皮癌の細胞間接着を抑制し，分散能を亢進することを報告し，さらに，癌細胞の増殖能の亢進も認めることを示してきた．今回，プラスミンによるE-カドヘリンのプロセシングに伴いβ-カテニンが細胞質に蓄積することで核内に移行し，細胞増殖を亢進している可能性が示されたことから，高い遺伝子導入効率で，安全なセンダイウイルベクターを用い，α2-アンチプラスミン遺伝子を腫瘍組織へ直接投与することで，癌の浸潤・転移を抑制しようとする本研究は，従来の外科手術や放射線治療にかわる安全性の高い口腔癌のin vivo遺伝子治療法の開発へ発展すると期待される.
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Report
(4 results)
Research Products
(13 results)
