Clarification of a role of sphingosine 1-phosphate in pathology of hepatocellular carcinoma, and its application for treatment strategy
| Project/Area Number |
16K09343
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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 |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Ikeda Hitoshi 東京大学, 医学部附属病院, 准教授 (80202422)
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| Research Collaborator |
Uranbileg Baasanjav
Yatomi Yutaka
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | スフィンゴシン1リン酸 / 肝細胞癌 / 大腸癌 / S1Pリアーゼ / トランスレーショナル・リサーチ / トランスレーショナルリサーチ / セラミド / 癌 / 脂質 / 臨床 |
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| Outline of Final Research Achievements |
Because sphingosine 1-phosphate (S1P) is a lipid mediator to be assumed to play a key role in cell growth and death, we examined potential roles of S1P in growth of hepatocellular carcinoma (HCC). Although the increase in intracellular S1P has been reported to be importantly involved in cell proliferation, mRNA expressions of not only a generating enzyme but also a degrading enzyme of S1P were enhanced in HCC tissues, and as a result, S1P was not increased in HCC tissues compared to non-cancerous tissues, suggesting that enhanced S1P metabolism but not increased intracellular S1P levels may play a pivotal role in HCC growth. Furthermore, our novel findings were similarly observed in colorectal cancer tissues, in which the theory showing a role of intracellular S1P levels on cell growth has been established.
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| Academic Significance and Societal Importance of the Research Achievements |
脂質メディエーターのS1Pは、その前駆物質であるセラミドとの細胞内のバランスが細胞増殖や生死の決定に重要であることが知られている。すなわち、S1Pの細胞内レベルが亢進すると、細胞は増殖し、アポトーシスは起こりにくくなるとされる。ところが、この現象を肝癌において検討したところ、分解酵素発現は亢進し、S1Pレベルの上昇は見られなかった。さらに大腸癌における検討により、S1Pの細胞内レベルではなく、代謝の亢進が細胞増殖に重要であることを発見した。この、従来の説を覆す知見に基づき、S1P代謝の抑制による癌治療の可能性が考えられる。さらに細胞のアポトーシスが原因とされる疾患の治療への応用も期待される。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Evidence Suggests Sphingosine 1-Phosphate Might Be Actively Generated, Degraded, and Transported to Extracellular Spaces With Increased S1P2 and S1P3 Expression in Colon Cancer.2017
Author(s)
Uranbileg B, Nishikawa T, Ikeda H, Kurano M, Sato M, Saigusa D, Aoki J, Watanabe T, Yatomi Y.
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Journal Title
Clin Colorectal Cancer.
Volume: Nov 21. pii:
Issue: 2
Pages: 30369-9
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence.2016
Author(s)
Uranbileg B, Ikeda H, Kurano M, Enooku K, Sato M, Saigusa D, Aoki J, Ishizawa T, Hasegawa K, Kokudo N, Yatomi Y.
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Journal Title
PLoS One
Volume: 11
Issue: 2
Pages: e0149462-e0149462
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.2016
Author(s)
Sato M, Ikeda H, Uranbileg B, Kurano M, Saigusa D, Aoki J, Maki H, Kudo H, Hasegawa K, Kokudo N, Yatomi Y.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 32119-32119
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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