| Project/Area Number |
17K15944
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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 |
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| Research Collaborator |
Hayashi Yoshito
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 大腸癌 / エクソソーム / 癌微小環境 / 癌関連線維芽細胞 / 下部消化管学 |
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| Outline of Final Research Achievements |
Tumor microenvironment offers favorable conditions for tumor progression and fibroblasts play a pivotal role. We aimed to elucidate the oncogenic role of cancer-derived exosomes (CDEs) in fibroblast modification and tumor growth. TP53-deficient colon cancer cells accelerated co-cultured fibroblast proliferation compared to control (TP53-wild colon cancer) cells in vitro. CDEs from TP53-deficient colon cancer cells suppressed TP53 expression of fibroblasts and promoted their proliferation. Xenografts of TP53-deficient colon cancer cells grew significantly faster than those of control cells in the presence of co-injected fibroblasts, but this difference was diminished by CDE inhibition. Several microRNAs, upregulated in TP53-deficient CDEs, were functionally proven to suppress TP53 expression in fibroblasts. Our results suggest that CDEs play a pivotal role in tumor progression via TP53 suppression of fibroblast. CDEs might represent a novel therapeutic target in colon cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
線維芽細胞は癌微小環境の中で腫瘍増大に中心的な役割を果たしており、なかでもp53遺伝子の抑制された線維芽細胞はより腫瘍増大に促進的な作用を有することが報告されている。今回、癌微小環境における線維芽細胞p53抑制機序として癌細胞由来エクソソーム中のいくつかのマイクロRNAが関わる可能性を見出した。これらのマイクロRNAの特異的阻害剤を導入することにより線維芽細胞のp53遺伝子発現がin vitroで回復する結果も得た。今後、これらのマイクロRNAが新規治療標的となりうる可能性が考えられる。
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