The mechanism of obesity-associated liver cancer progression through cytokine cross-talk in tumor microenvironment.
| Project/Area Number |
16H04699
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Osaka City University (2017-2018)
Tokyo University of Science (2016) |
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Principal Investigator |
Ohtani Naoko 大阪市立大学, 大学院医学研究科, 教授 (50275195)
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| Co-Investigator(Kenkyū-buntansha) |
蒲池 史卓 大阪市立大学, 大学院医学研究科, 講師 (00747800)
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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 |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2018: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | がん微小環境 / 細胞老化随伴分泌現象 / IL-33 / 制御性T細胞 / 肥満関連肝がん / 肝星細胞 / 細胞老化 / SASP / 肥満誘導性肝がん / 炎症性サイトカイン |
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| Outline of Final Research Achievements |
In this study, we found that IL-33 is highly expressed in the obesity-associated liver tumor region particularly in the senescent hepatic stellate cells. The released IL-33 stimulates its receptor-positive Treg cells, thereby contributing the suppression of antitumor immunity and the progression of the obesity-associated HCC. We discovered a novel mechanism of the export of senescence-associated secretory proteins from senescent hepatic stellate cells to suppress anti-tumor immunity in the liver tumor microenvironment.
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| Academic Significance and Societal Importance of the Research Achievements |
IL-33をプロセシングし、活性化型にするプロテアーゼもIL-33の発現細胞で同時にSASP因子として発現していることがわかり、SASP因子同士の協調作用という興味深い新規知見を得ることができた。また、IL-33を含むSASP因子が老化肝星細胞から放出される分子機構を明らかにし、SASP因子の放出抑制が癌抑制につながる可能性を見出した。本研究により腸炎やアレルギーだけでなく、がん進展にIL-33-ST2経路が関与することが明らかになり、この経路が抗腫瘍免疫を標的とした新規がん治療法の開発につながる可能性がある。
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Epidermal growth factor receptor is a host entry cofactor triggering hepatitis B virus internalization2019
Author(s)
M. Iwamoto, W. Saso, R. Sugiyama, K. Ishii, M. Ohki, S. Nagamori, R. Suzuki, H. Aizaki, A. Ryo, J-H Yun, S-Y Park, N. Ohtani, M. Muramatsu, S. Iwami, Y. Tanaka, C. Sureau, T. Wakita and K. Watashi
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 116
Issue: 17
Pages: 8487-8492
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells2018
Author(s)
Takahashi A, Loo TM, Okada R, Kamachi F, Watanabe Y, Wakita M, Watanabe S, Kawamoto S, Miyata K, Barber GN, Ohtani N, Hara E
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 1249-1249
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide2018
Author(s)
Kaneko M, Futamura Y, Tsukuda S, Kondoh Y, Sekine T, Hirano H, Fukano K, Ohashi H, Saso W, Morishita R, Matsunaga S, Kawai F, Ryo A, Park S-Y, Suzuki R, Aizaki H, Ohtani N, Sureau C, Wakita T, Osada H, Watashi K
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 2769-2769
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity.2017
Author(s)
Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo MM, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N.
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Journal Title
Cancer Discov
Volume: 7
Pages: 522-538
Related Report
Peer Reviewed
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[Journal Article] Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity.2017
Author(s)
Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo M, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N.
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Journal Title
Cancer Discov
Volume: in press
Issue: 5
Pages: 522-538
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] IL-33/ST2 pathway promotes obesity-associated liver cancer development2017
Author(s)
Fumitaka Kamachi, Masaru Nakamura, Shota Yamazaki, Tze Mun Loo, Shin Yoshimoto, Tatsuya Arai, Yohsuke Harada, Masato Kubo, Susumu Nakae, Eiji Hara, Naoko Ohtani
Organizer
The 19h Takeda Science Foundation Symposium on Biosciences
Place of Presentation
Suita, Osaka, Japan
Year and Date
2017-01-20
Related Report
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[Presentation] Synergism of SASP factors: activation mechanism of interleukin-33 in senescent hepatic stellate cells in promoting obesity-associated liver cancer2017
Author(s)
Shota Yamazaki, Fumitaka Kamachi, Masaru Nakamura, Masahiro Nakajima, Tze Mun Loo, Shin Yoshimoto, Tatsuya Arai, Hayao Taguchi, Susumu Nakae, Eiji Hara, Naoko Ohtani
Organizer
The 19h Takeda Science Foundation Symposium on Biosciences
Place of Presentation
Suita, Osaka, Japan
Year and Date
2017-01-20
Related Report
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