2021 Fiscal Year Final Research Report
Elucidation of the mechanism of tumorigenesis by the interaction between hepatic stellate cells and hepatocytes in the cancer microenvironment.
Project/Area Number |
20K16163
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 49010:Pathological biochemistry-related
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Research Institution | Japanese Foundation for Cancer Research |
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) |
2020-04-01 – 2022-03-31
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Keywords | 脂肪肝 / 代謝 / 細胞老化 |
Outline of Final Research Achievements |
Our previous studies have found that senescent hepatic stellate cells are involved in the development of obesity-induced liver cancer. However, the involvement of interaction between senescent hepatic stellate cells and hepatocytes remains unclear. We cultured hepatocytes and hepatic stellate cells in the environment that mimics a fatty liver and found that the expression of genes involved in lipid metabolism largely changed. Moreover, we successfully isolated hepatic stellate cells and hepatocytes from mouse fatty livers to investigate this cell-cell interaction. Furthermore, inhibiting lipid accumulation in the hepatocytes of obese mice suppressed the formation of liver tumors. These results suggest that aged hepatic stellate cells regulate the metabolism of hepatic parenchymal cells and promote the formation of liver tumors.
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Free Research Field |
腫瘍生物学
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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ける肝実質細胞と肝星細胞が異なる脂質代謝の状態を呈していることを見出し、それらが肝腫瘍の脂質の蓄積を引き起こし、肝がんの発症を促すという知見を得ることができた。このことはがん微小環境内における細胞間の相互作用によるがんの発症の基本メカニズムの解明に繋がる成果である。また、本研究により申請者はマウスの脂肪肝から肝星細胞と肝実質細胞を単離する系を構築しており、より生体に近い状態で詳細な細胞の解析が可能になったことから、今後肥満誘導性肝がんに対して有効な治療法や予防法の開発につながる可能性が期待される。
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