| Project/Area Number |
17K16543
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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 |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
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| Research Collaborator |
Noda Takehiro
Eguchi Hidetoshi
Iwagami Yoshifumi
Yamada Daisaku
Akita Hirofumi
Asaoka Tadafumi
Kawamoto Koichi
Gotoh Kunihito
Kobayashi Syogo
Mori Masaki
Doki Yuichiro
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肝細胞癌 / 肝内転移 / 転移メカニスズム / In vivo selection / 統合プロファイリング / 網羅的遺伝子解析 / 転移メカニズム / 総合プロファイリング |
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| Outline of Final Research Achievements |
The aim of this study is to investigate the mechanism of intrahepatic metastasis in HCC. Highly intrahepatic metastatic HCC cell line (HuH-7) was established by in vivo selection using trans-portal vein metastatic model. After tumor dissociation and expansion in culture, the resulting cell populations were subjected to the next cycle. After 4 cycles, highly intrahepatic metastatic cell and parent cell were compared in vitro and in vivo. Proliferative potential was increased and apoptosis was suppressed (13.4% vs 3.4%). In addition, tumorigenesis was exacerbated. Subsequently, integrated microarray analysis was performed to identify the target molecules. Integrated expression profiling of miRNA and mRNA was analysed. As a result, miR23a-3p was selected as a target miRNA; VCAN and CXCL12 were selected as target mRNAs.
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| Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌に対する主な治療法は外科的手術であるが, 5年生存率は約40%とその治療成績は極めて不良である. 肝細胞癌が予後不良である原因の一つとして, 根治的切除しえたとしても術後の肝内転移が高率で起こることが挙げられる. 本研究はマウスを用いて人為的に高肝内転移能株を作成し, 親株と併せて網羅的遺伝子解析を行うことで治療ターゲットの同定を試み, その結果有望なmRNAおよびmiRNAを同定した.
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