2019 Fiscal Year Final Research Report
A search for the characteristic molecules of oral squamous cell carcinoma stem cells using reprogramming technic.
| Project/Area Number |
19K21387
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| Project/Area Number (Other) |
18H06299 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0907:Oral science and related fields
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| Research Institution | The Nippon Dental University |
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Principal Investigator |
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Keywords | 癌幹細胞 / リプログラミング / iPS細胞 / 口腔扁平上皮癌 |
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| Outline of Final Research Achievements |
The aim of this study is to clarify the molecules of oral squamous cell carcinoma stem cells. To generate CSC-like cells in vitro, we transduced four previously established reprogramming factors, Oct3/4, Sox2, Klf4, and L-myc, into the oral squamous cell carcinoma cell lines HSC-3-M3, KON and Ca9-22. CSC markers such as CD133 and ALDH1 expression were upregulated after reprogramming, but did not showed CSC properties, including colony formation, maintenance of colonies by repeated passages.To overcome these problems, Tra-1-60+ cells were obtained from reprogrammed cells, and showed CSC properties, including colony formation, maintenance of colonies by repeated passages, as well as increased expressions of CSC markers such as CD90/Thy-1 and CD44.Our results show that reprogramming of oral cancer cells produced not pluripotent stem cells but CSC-like cells, and these findings will provide biological information about genuine CSCs and help establish new CSC-targeted therapies.
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| Free Research Field |
腫瘍生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によってリプログラミング口腔癌細胞を継続培養する手法を確立できたことは、今後の口腔癌幹細胞研究のみならず扁平上皮がんに対する治療標的分子の探索に、学術的に大きな意義がある。
また、進行がんの根治が困難な主な原因は転移と再発であり、自己増殖能、多分化能、薬剤耐性能を持ったがん幹細胞(CSC) を対象とする研究が盛んに行われているが、今なお多くのがんにおいてCSCは未同定である。本研究の成果によって、人工的に作り出したCSC様細胞を詳細に解析し、実在のCSCの性質を予測する研究を発展させることができ、CSCを標的としたがん治療法の開発に向け、社会的意義があると考えている。
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