2018 Fiscal Year Final Research Report
Analysis of the induced cancer stem-like sphere cells-specific molecules to prevent the metastatic properties of hepatocellular carcinom
| Project/Area Number |
16K10574
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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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| Research Field |
Digestive surgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 癌 |
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| Outline of Final Research Achievements |
Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) from hepatoma cell lines using a unique medium. Our induced CSLCs showed characteristic phenotypes of CSCs such as chemo- and immune-resistances. As a result of integrated analysis with RNA-seq, a RAB3B was identified as an up-regulated gene in both CSLCs in vitro and poor prognostic HCCs in vivo. Cells harboring mono-allelic RAB3B knock-out showed altered sphere formation and significantly lower chemoresistance compared to those of parental cells. The mono-allelic RAB3B knock-out cells also showed decreased PD-1 ligands in sphere induction medium than those in cells cultured with normal medium. Therefore, the up-regulation of RAB3B may plays important roles in CSLCs.
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| Free Research Field |
腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究から，がん幹細胞特性，特に治療抵抗性及び転移能に関与する遺伝子としてRAB3Bを同定した．また，本研究における大量調製可能な誘導がん幹細胞が，免疫逃避機構も備えることが新たに明らかとなり，がん幹細胞を標的としたさらなる免疫療法の開発への展開が可能となった．本研究は，がんの予後不良の主因とも言える術後再発を抑制するための意義ある成果をもたらした．
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