| Project/Area Number |
17K15943
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
Yuki Makino 大阪大学, 医学部附属病院, 医員 (60771334)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝細胞癌 / CTGF / 肝星細胞 / 腫瘍間質反応 / 抗体療法 |
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| Outline of Final Research Achievements |
In surgically resected hepatocellular carcinoma (HCC) samples, CTGF was up-regulated in tumorous tissues compared with non-tumorous liver tissues. CTGF expression levels were correlated with the malignant grade of HCC.
CTGF was also overexpressed in liver tumors in Kras-mutated HCC model mice. In these mice, CTGF deletion attenuated tumor development.
Cell culture experiments revealed that CTGF mediates tumor-stroma interactions between HCC cells and hepatic stellate cells to promote HCC progression. CTGF-mediated tumor-stroma interaction could be inhibited by an anti-CTGF neutralizing antibody treatment. Therefore, an anti-CTGF neutralizing antibody was shown to be a novel therapeutic agent for HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌は本邦における癌による死亡の第５位を占める難治癌である。薬物療法は肝細胞癌の治療選択肢の一つであるが、現在本邦において使用可能な薬剤の有効性は十分とはいえず、新規薬剤の登場が望まれている。
本研究課題により、CTGFに対する中和抗体が肝癌細胞と肝星細胞の腫瘍間質反応を阻害する作用を有することが明らかとなり、肝細胞癌に対する新規薬剤に成り得ることが示された。CTGF中和抗体は膵癌に対して既に臨床試験が行われており、今後肝癌に対しても臨床応用が進められることが期待される。
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