Elucidation of the molecular basis for the cancer stem cell niche
| Project/Area Number |
15H04292
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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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| Research Field |
Tumor biology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TAGA Tetsuya 東京医科歯科大学, 難治疾患研究所, 教授 (40192629)
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| Research Collaborator |
BRADLEY Mark University of Edinburgh, School of Chemistry, Professor
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| Keywords | 癌 / 癌幹細胞 / ニッチ / グリオーマ / 膵臓癌 / ヘム / 鉄 / 5-ALA / プロトポルフィリンIX / ミトコンドリア / シグナル伝達 |
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| Outline of Final Research Achievements |
Cancer stem cells (CSCs) reside in a microenvironment, niche. Elucidation of the CSC niche helps develop new cancer therapy. We have identified a CSC niche-mimicking polymer from 376 synthetic polymers and identified an iron-carrier transferrin (Tf) which binds to it. In the tumor formed in the mouse brain following transplantation of rat C6 glioma CSCs, iron was found to be stored in tumor-associated macrophages (TAMs), suggesting contribution of iron-storing TAMs to cancer progression. We further demonstrated that CSCs recruit monocytes and induce their differentiation into TAMs. Since PpIX, a fluorescent metabolite of 5-ALA, accumulates in glioma cells, 5-ALA is used for fluorescence-guided surgical resection. We indicated that CSCs exhibit low PpIX accumulation among glioma cells via nonfluorescent conversion by iron incorporated by Tf receptor, suggesting that CSCs escape from surgical resection. We propose that glioma CSCs have a capacity to construct self-advantageous niche.
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] A synthetic polymer scaffold reveals the self-maintenance strategies of rat glioma stem cells by organization of the advantageous niche.2016
Author(s)
Tabu K, Muramatsu N, Mangani C, Wu M, Zhang R, Kimura T, Terashima K, Bizen N, Kimura R, Wang W, Murota Y, Kokubu Y, Nobuhisa I, Kagawa T, Kitabayashi I, Bradley M, Taga T.
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Journal Title
Stem Cells
Volume: 34
Issue: 5
Pages: 1151-1162
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Identification and analysis of CXCR4-positive synovial sarcoma initiating cells.2016
Author(s)
Kimura T, Wang L, Tabu K, Tsuda M, Tanino M, Maekawa A, Nishihara H, Hiraga H, Taga T, Oda Y, Tanaka S.
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Journal Title
Oncogene
Volume: 未定
Issue: 30
Pages: 3932-3943
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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