Targeting the Cancer Stem Cell in Vascular Niche for Oral Cancer Therapy
| Project/Area Number |
20K10175
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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 | Hokkaido University |
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Principal Investigator |
Satoh Chiharu 北海道大学, 大学病院, 講師 (50222013)
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| Co-Investigator(Kenkyū-buntansha) |
菊地 奈湖 (間石奈湖) 北海道大学, 歯学研究院, 助教 (00632423)
ANNAN DORCAS・AKUBAMUHYIA 北海道大学, 歯学研究院, 学術研究員 (30837240)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | がん幹細胞 / 血管ニッチ / 口腔がん / 腫瘍血管内皮細胞 |
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| Outline of Research at the Start |
がん幹細胞は，高い自己複製能や薬剤耐性を示すため，抗がん剤治療や放射線治療への抵抗性が高く，がんの再発に密接に関係している．したがって，がん幹細胞を制御することががん治療の重要な課題である．
近年，がん幹細胞は血管の近傍に局在することが報告されている．しかし，口腔がんにおけるがん幹細胞のすみか，いわゆるがん幹細胞ニッチの形成メカニズムについてはいまだ不明である．
本研究では，口腔がん幹細胞の維持における血管の役割を明らかにし，口腔がん幹細胞血管ニッチを標的とした新しいがん治療法開発のための基盤的研究を行う．
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| Outline of Final Research Achievements |
Cancer stem cells co-cultured with tumor endothelial cells showed increased expression of cancer stem cell markers. These cells are resistant to anticancer drugs. When the expression of molecules highly expressed in tumor endothelial cells was suppressed, the expression of stem cell markers in the co-cultured cancer stem cells was decreased. The drug resistance to anticancer drugs was also weakened. In tumor tissues, cancer stem cell marker-positive cells were observed in the vicinity of tumor blood vessels. Among tumor blood vessels, cancer stem cells tended to be localized in the vicinity of vessels with high expression of tumor endothelial cell marker-positive blood vessels. The relationship between their expression and clinicopathological factors and prognosis are under investigation.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの難治性に起因するがん幹細胞に関する研究は，現在広く行われている．しかし，腫瘍血管に着目したがん幹細胞研究はほとんど報告がない．がん細胞およびがん幹細胞だけを標的としても，それを養う腫瘍血管が残っていれば，がん幹細胞をサポートし，わずかに残ったがん幹細胞が増殖してがんの再発や転移につながる．がんを根治するためには，がん細胞，がん幹細胞のみなならず，腫瘍血管も標的とする必要があり，また本研究は口腔がんのみならず，多くのがんに共通したがん幹細胞標的化戦略に有用であることが期待される．
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] miR-1246 in tumor extracellular vesicles promotes metastasis via increased tumor cell adhesion and endothelial cell barrier destruction2023
Author(s)
Morimoto M, Maishi N, Tsumita T, Alam MT, Kikuchi H, Hida Y, Yoshioka Y, Ochiya T, Annan DA, Takeda R, Kitagawa Y, Hida K
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The oral bacterium Streptococcus mutans promotes tumor metastasis by inducing vascular inflammation2022
Author(s)
Yu L, Maishi N, Akahori E, Hasebe A, Takeda R, Yanagawa-Matsuda A, Hida Y, Nam Jin-Min, Onodera Y, Kitagawa Y, Hida K*
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Journal Title
Cancer Sci
Volume: 113
Issue: 11
Pages: 3980-3994
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel antiangiogenic therapy targeting biglycan using tumor endothelial cell-specific liposomal siRNA delivery system2022
Author(s)
Maishi N, Sakurai Y, Hatakeyama H, Umeyama Y, Nakamura T, Endo R, Alam MT, Li C, Annan DA, Kikuchi H, Morimoto H, Morimoto M, Akiyama K, Ohga N, Hida Y, Harashima H, *Hida K
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Correlation between endothelial chemokine receptor 7CXCR7 expression and clinicopathological factors in oral squamous cell carcinoma2021
Author(s)
Yanagiya M, Dawood RIH, Nako Maishi N, Yasuhiro Hida Y, Chisaho Torii C, Hiroshi Kikuchi H, Aya Yanagawa, Matsuda A, Tetsuya Kitamura T, Tei K, Shindoh M, Tanaka S, Kitagawa Y, Hida K
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Journal Title
Pathology International
Volume: 71（5）
Related Report
Peer Reviewed
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