Liver cancer cells manipulate stromal cells involved in fibrosis to promote tumor growth
| Project/Area Number |
19K17489
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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 53010:Gastroenterology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Yuta Myojin 大阪大学, 医学部附属病院, 医員 (20838817)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 肝細胞癌 / 肝星細胞 / GDF15 / 単一細胞解析 / 癌微小環境 / シングルセルシークエンス |
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| Outline of Research at the Start |
癌細胞は微小環境を自身の増殖に有利に変化させて発育進展する。肝癌では星細胞が存在し、微小環境形成に寄与している可能性がある。最近申請者は、肝癌細胞と共培養した星細胞ではオートファジーが促進することを見出した。このオートファジー亢進を抑制すると、共培養した肝癌細胞の増殖速度が低下するという予備的結果を得ている。そのため、肝星細胞のオートファジーが肝細胞癌に対する新規治療標的となる可能性がある。本申請課題では、肝星細胞におけるオートファジーが癌微小環境を通じて肝癌細胞にあたえる細胞間コミュニケーションの分子基盤を解明し、肝癌細胞増殖にあたえる新規メカニズムの解明を目的として研究を行う。
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| Outline of Final Research Achievements |
Hepatocellular carcinoma (HCC), frequently seen in patients with liver cirrhosis caused by alcohol abuse or chronic viral hepatitis, is the most common form of liver cancer worldwide. As such, it is the third-most common cause of cancer-related death and has a notoriously poor prognosis. At present, surgery is the most effective treatment for HCC, but is only successful in the 10-20% of cases where cancer cells have not spread beyond the liver. We have found that liver cancer cells induce autophagy in hepatic stellate cells, causing them to produce a growth factor called GDF15 that promotes tumor growth. GDF15 was more highly expressed in tumor tissue than normal liver tissue, and patients with higher levels of GDF15 had a poorer prognosis. New therapies targeting GDF15 may help prevent the development and proliferation of hepatocellular carcinoma.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで明らかでなかった肝星細胞と肝がん細胞の相互作用について今後より研究が発展することが望まれます。今後GDF15に対する中和抗体などGDF15を標的とした治療が、肝がん患者さんに対する新たな治療選択肢の1つとして臨床開発されることが期待されます。
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Hepatic Stellate Cells in Hepatocellular Carcinoma Promote Tumor Growth Via Growth Differentiation Factor 15 Production2021
Author(s)
Myojin Y, Hikita H, Sugiyama M, Sasaki Y, Fukumoto K, Sakane S, Makino Y, Takemura N, Yamada R, Shigekawa M, Kodama T, Sakamori R, Kobayashi S, Tatsumi T, Suemizu H, Eguchi H, Kokudo N, Mizokami M, Takehara T.
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Journal Title
Gastroenterology .
Volume: 160
Issue: 5
Pages: 1741-1754
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Hepatic stellate cell autophagy promotes HCC progression via GDF152020
Author(s)
Yuta Myojin, Hayato Hikita, Masaya Sugiyama, Takahiro Kodama, Yuki Makino, Ryoko Yamada, Tasuku Nakabori, Ryotaro Sakamori, Tomohide Tatsumi, Masashi Mizokami, Tetsuo Takehara
Organizer
The Digital International Liver Congress of the European Association for the Study of the Liver
Related Report
Int'l Joint Research
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[Presentation] Hepatic stellate cell autophagy promotes HCC progression via GDF152020
Author(s)
Yuta Myojin, Hayato Hikita, Masaya Sugiyama, Takahiro Kodama, Yuki Makino, Ryoko Yamada, Tasuku Nakabori, Ryotaro Sakamori, Tomohide Tatsumi, Masashi Mizokami, Tetsuo Takehara
Organizer
The 55th International Liver Congress of the EASL
Related Report
Int'l Joint Research
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