Carcinogenic mechanisms of stem cells in inflammation-related cancer and its prevention
| Project/Area Number |
16H05255
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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 |
Hygiene and public health
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| Research Institution | Mie University |
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Principal Investigator |
Murata Mariko 三重大学, 医学系研究科, 教授 (10171141)
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| Co-Investigator(Kenkyū-buntansha) |
及川 伸二 三重大学, 医学系研究科, 准教授 (10277006)
翠川 薫 三重大学, 医学系研究科, リサーチアソシエイト (20393366)
平工 雄介 福井大学, 学術研究院医学系部門, 教授 (30324510)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | がん / 炎症 / 幹細胞 / 8-ニトログアニン / エピゲノム異常 / CD44v9 / HMGB1 / 炎症関連発がん / DNA損傷 / 癌 / 遺伝子損傷 |
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| Outline of Final Research Achievements |
Under chronic inflammation, reactive oxygen / nitrogen species are produced from both inflammatory cells and epithelial cells. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-nitroguanine, accumulation of mutation, and epigenetic alteration. Tissue injury may activate stem cells for tissue regeneration under inflammatory microenvironment.
We demonstrated that indium compounds induced inflammation-specific 8-nitroguanine formation in lung epithelial cells via HMGB1-RAGE pathway. We found the formation of 8-nitroguanine in stem cell marker CD44v6 and ALDH1A1-positive cancer cells. Liker fluke-infested cholangiocarcinoma (CCA) exhibited a higher level of CD44v9 expression than in sporadic CCA tissues, and no CD44v9 staining in the normal bile duct cells. We observed significantly higher expression of inflammation-related markers, S100P and COX-2, in liker fluke-infested CCA tissues. It is suggested that inflammation may associate cancer stem cells.
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| Academic Significance and Societal Importance of the Research Achievements |
感染症および慢性炎症が全世界の発がん要因の約25%を占めると推定されている。本研究の成果として、炎症が幹細胞がん化に寄与する可能性が示されたことは、抗炎症物質ががん予防に有効である疫学研究結果を支持するものであり、学術的意義は高い。また、炎症を促進する経路のリガンドとしてHMGB1やS100Pの寄与を明らかにしており、これらを標的とする創薬がなされれば、社会的意義は大きい。
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Report
(4 results)
Research Products
(105 results)
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[Journal Article] Oxidative DNA damage induced by pirarubicin, an anthracycline anticancer agent, in the presence of copper(II).2018
Author(s)
Mizutani H, Nishimoto A, Hotta S, Ikemura K, Imai M, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
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Journal Title
Anticancer Research
Volume: 38
Issue: 5
Pages: 2643-2648
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through Generation of Hydrogen Peroxide.2017
Author(s)
Mizutani H, Hotta S, Nishimoto A, Ikemura K, Miyazawa D, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S.
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Journal Title
Anticancer Res.
Volume: 37
Issue: 11
Pages: 6063-6069
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] APOE Genotype in the Ethnic Majority and Minority Groups of Laos and the Implications for Non-Communicable Diseases.2016
Author(s)
Midorikawa K, Soukaloun D, Akkhavong K, Southivong B, Rattanavong O, Sengkhygnavong V, Pyaluanglath A, Sayasithsena S, Nakamura S, Midorikawa Y, Murata M.
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Journal Title
PLoS One
Volume: 11
Issue: 5
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Epigenetic inactivation of follistatin-like 1 mediates tumor immune evasion in nasopharyngeal carcinoma.2016
Author(s)
Zhou X, Xiao X, Huang T, Du C, Wang S, Mo Y, Ma N, Murata M, Li B, Wen W, Huang G, Zeng X, Zhang Z
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Journal Title
Oncotarget
Volume: 7
Issue: 13
Pages: 16433-16444
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS.2016
Author(s)
He F, Wei L, Luo W, Liao Z, Li B, Zhou X, Xiao X, You J, Chen Y, Zheng S, Li P, Murata M, Huang G, Zhang Z
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Journal Title
Oncotarget.
Volume: 7
Issue: 24
Pages: 37000-37012
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Exposure assessment and heart rate variability monitoring in workers handling titanium dioxide particles-a pilot study.2016
Author(s)
Ichihara S, Li W, Omura S, Fujitani Y, Liu Y, Wang Q, Hiraku Y, Hisanaga N, Wakai K, Ding X, Kobayashi T, Ichihara G.
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Journal Title
J. Nanopart. Res.
Volume: 18
Issue: 3
Pages: 52-52
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] PRKCB, a tumor suppressor, is epigenetically inactivated in nasopharyngeal carcinoma2016
Author(s)
Weilin Zhao, Shumin Wang, Kaoru Midorikawa, Zhe Zhang, Yingxi Mo, Guangwu Huang, Ning Ma, Yusuke Hiraku, Shinji Oikawa, Kazuhiko Takeuchi, Mariko Murata.
Organizer
第75回日本癌学会総会
Place of Presentation
パシフィコ横浜（神奈川県横浜市）
Year and Date
2016-10-06
Related Report
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[Presentation] Tumor suppressing roles of let-7c in head and neck cancer.2016
Author(s)
Bo Hou, Hajime Ishinaga, Kaoru Midorikawa, Ning Ma, Weilin Zhao, Shinji Oikawa, Yusuke Hiraku, Kazuhiko Takeuchi, Mariko Murata
Organizer
The 7th EMBO meeting 2016
Place of Presentation
Congress Center Rosengarten Mannheim（Mannheim,Germany)
Year and Date
2016-09-10
Related Report
Int'l Joint Research
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