The role of senescent cell-derived exosomes in obesity-induced liver cancer
| Project/Area Number |
18K15073
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
LOO TZE MUN 公益財団法人がん研究会, がん研究所 細胞老化プロジェクト, 研究員 (40816998)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 脂肪肝 / 代謝 / 細胞老化 / 肥満誘導性肝癌 / エクソソーム |
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| Outline of Final Research Achievements |
Recently various studies and epidemiological studies have pointed out that obesity promotes the development of cancer. As one of the mechanisms for developing liver cancer caused by obesity, we were focusing on cellular senescence of hepatic stellate cells and reported that senescent hepatic stellate cells promote the development of liver cancer. However, the molecular mechanisms of senescent hepatic stellate cells to cause the malignant alteration of hepatocyte is still unknown. On the other hand, various studies have reported that extracellular secretory vesicles secreted from cells promote tumorigenesis. Therefore, in this study, we analyzed the extracellular secretory vesicles secreted by senescent hepatic stellate cells that cause the malignant transformation of hepatocyte.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究から、申請者は肥満誘導性肝がんモデルマウスの腫瘍部において著しい代謝変化が起きていることを明らかにした。更に、申請者脂肪肝を模した条件下で肝星細胞を培養したところ、肝星細胞における細胞外分泌小胞の分泌量が増加することがわかった。また、脂肪肝を模した条件で肝星細胞株と肝臓がん細胞株を共培養したところ、細胞における代謝遺伝子の発現パターンが変化することを明らかにした。このことから、肝腫瘍内にこれらの細胞が細胞外分泌小胞を介して相互作用し、細胞の代謝経路に影響を与えていることが示唆された。そのため、細胞老化を起こした肝星細胞を標的した新規の肝がん治療法や予防法の開発につながる可能性がある。
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Report
(3 results)
Research Products
(2 results)
