Investigation of radio-resistant mechanism of well differentiated adenocarcinoma using a primary culture system, CTOS
| Project/Area Number |
16K10414
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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 |
Radiation science
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| Research Institution | Osaka International Cancer Institute |
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Principal Investigator |
Endo Hiroko 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 主任研究員 (20359300)
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| Co-Investigator(Kenkyū-buntansha) |
井上 正宏 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 特別研究員 (10342990)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 放射線感受性 / 分化型腺癌 / 三次元培養系 / 大腸癌 / 放射線腫瘍学 |
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| Outline of Final Research Achievements |
We examined the effect of stem/differentiation status on radio-sensitivity of well-differentiated colorectal cancer using three-dimensional culture system, CTOS (Cancer Tissue-Originated Spheroid). We found that the stem/differentiation status of colorectal cancer CTOS was highly fluctuated by the difference in culture conditions or the stimulation of mechanical disruption. CTOSs with high Wnt signaling were resistant to X-ray irradiation. Pre-treatment of CTOS with HDAC inhibitors resulted in the downregulation of stemness genes and enhanced radio-sensitivity. These results indicated that HDAC inhibitors could be a radio-sensitizer for colorectal cancer though attenuating the stemness of well differentiated adenocarcinoma.
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| Academic Significance and Societal Importance of the Research Achievements |
正常組織における分化/幹細胞の階層性が放射線感受性に与える影響は、トランスジェニックマウスを用いた研究で多く報告されている。しかし、大腸がんをはじめとする分化型腺癌の幹細胞性と放射線感受性に関しては、あまり研究されてこなかった。その理由のひとつとして、分化型腺癌の特徴を保持した実験系が存在しなかったことが挙げられる。今回、我々は三次元培養系CTOS法を用いて、大腸癌細胞の分化/幹細胞性が大きく揺らぐこと、その中でもWntシグナルが高い状態にある癌細胞が放射線耐性を示すことを見出した。CTOS法は、分化型腺癌を対象とした放射線増感剤の研究プラットフォームとなりうる。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Promotion of malignant phenotype after disruption of the three-dimensional structure of cultured spheroids from colorectal cancer.2018
Author(s)
Piulats JM, Kondo J, Endo H, Ono H, Hagihara T, Okuyama H, Nishizawa Y, Tomita Y, Ohue M, Okita K, Oyama H, Bono H, Masuko T, Inoue M.
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Journal Title
Oncotarget
Volume: 9
Issue: 22
Pages: 15968-15983
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition.2017
Author(s)
Goodwin J, Neugent ML, Lee SY, Choe JH, Choi H, Jenkins DMR, Ruthenborg RJ, Robinson MW, Jeong JY, Wake M, Abe H, Takeda N, Endo H, Inoue M, Xuan Z, Yoo H, Chen M, Ahn JM, Minna JD, Helke KL, Singh PK, Shackelford DB, Kim JW.
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Journal Title
Nature Communications
Volume: 8
Issue: 1
Pages: 15503-15503
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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