| Project/Area Number |
19K09218
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
新藤 芳太郎 山口大学, 大学院医学系研究科, 助教 (70749811)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 癌 |
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| Outline of Research at the Start |
予後不良なHCCを対象として、転移の原因となる癌幹細胞 (CSC) を解析し、肝内転移による術後再発の抑制に結びつける。我々は、癌幹細胞様浮遊細胞塊 (Cancer stem-like sphere cells, CSLCs) を独自誘導し、分泌に関わるRAB3B等の特異的遺伝子を同定しており、本研究により術後肝内転移抑制のコンセプトを確立する。
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| Outline of Final Research Achievements |
To development of targeting therapy against cancer stem-like cells (CSLCs), we examined therapy resistance of CSLCs and identified a responsible gene for the CSLC phenotype. Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique medium. To assess the chemoresistance and liver metastasis, MTS assay and splenic injection were performed. Expressional analyses were performed using RNA-seq, qPCR, flow-cytometry, and ELISA.
The obtained CSLCs showed increased chemoresistance and metastatic potentials. A RAB3B was identified as an up-regulated gene in both CSLCs and poor prognostic HCCs by RNA-seq. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, cell cycle, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion in CSLCs were not observed in the RAB3B-KO cells.
It was suggested that the up-regulation of RAB3B plays important roles in CSLCs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、肝癌幹細胞様細胞 (cancer stem-like sphere cell; CSLC)のsphere形成能、化学療法抵抗性や転移能において、RAB3Bのアップレギュレーションが重要な役割を担っていることが示された。癌の転移・再発において重要な役割を果たす癌幹細胞に対する有望な治療標的としてRAB3Bが有望であることを示唆する学術的・社会的に意義ある成果を得た。
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