Organoid-based Modeling of Endometrial Carcinogenesis
| Project/Area Number |
17K19624
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Chiba Cancer Center (Research Institute) |
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Principal Investigator |
Hippo Yoshitaka 千葉県がんセンター(研究所), 発がん制御研究部, 部長 (30359632)
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| Co-Investigator(Kenkyū-buntansha) |
丸 喜明 千葉県がんセンター(研究所), 発がん研究グループ 発がん制御研究部, 研究員 (30742754)
田中 尚武 千葉県がんセンター(研究所), 婦人科, 部長 (80236611)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 子宮がん / オルガノイド / 癌肉腫 / 転移 / Kras / Pten / マウス / 子宮体がん / 子宮内膜がん / 発がん / モデル / がん肉腫 / 癌 / 子宮 / 遺伝子 |
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| Outline of Final Research Achievements |
Pten knockdown in mouse endometrial organoids did not result in tumorigenesis in nude mice when inoculated, either alone or in combination with Kras mutations. In contrast, Kras mutation combined with suppression of Cdkn2a expression or deletion of p53 induced carcinosarcoma in all cases. The combination of Kras mutation and suppression of Pten expression induced adenocarcinoma only when long-term cultured organoids were used, but simultaneously acquired lymph node metastaticity. Evaluation of gene copy number by array CGH identified a stepwise deletion of gene X during long-tgerm culture and tumorigenesis. The Kras mutation combined with the deletion of gene X indeed formed a cancer with adenosquamous carcinoma histology, and the combination of Pten or Cdkn2a expression repression further induced metastasis. Collectively, we demonstrated that organoid-based carcinogenesis model served as apoewrful tool in elucidataing the mechanisms underlying endometrial carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
従来発がんモデルとしては遺伝子改変マウスが汎用されていたが、時間と労力を要するために、特に子宮体がんに関してはモデル作成が進んでいなかった。我々はマウス子宮内膜オルガノイドへの遺伝子導入により迅速かつ簡便に発がんモデルを作成することを試み、実際に複数の組み合わせで腫瘍形成に成功した。遺伝子改変マウスとは異なる結果になる場合や新規に転移を伴う腫瘍を作成するなど、子宮体がんの発がん機構に関する新規の洞察を得ることができた。治療法の開発に有用なモデルになると考えられた。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix2020
Author(s)
Maru Y, Kawata A, Taguchi A, Ishii Y, Baba S, Mori M, Nagamatsu T, Oda K, Kukimoto I, Osuga Y, Fujii T, Hippo Y.
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Journal Title
Cancers
Volume: 12
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis.2018
Author(s)
Enjoji S, Yabe R, Tsuji S, Yoshimura K, Kawasaki H, Sakurai M, Sakai Y, Takenouchi H, Yoshino S, Hazama S, Nagano H, Oshima H, Oshima M, Vitek MP, Matsuura T, Hippo Y, Usui T, Ohama T*, Sato K
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Journal Title
Mol Cancer Res
Volume: 16
Issue: 3
Pages: 554-563
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells.2017
Author(s)
Sato T, Morita M, Tanaka R, Inoue Y, Nomura M, Sakamoto Y, Miura K, Ito S, Sato I, Tanaka N, Abe J, Takahashi S, Kawai M, Sato M, Hippo Y, Shima H, Okada Y, Tanuma N
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Journal Title
Oncol Lett
Volume: 14(6)
Pages: 6863-6868
DOI
Related Report
Peer Reviewed / Open Access
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[Book] 進化するがん創薬2019
Author(s)
清宮 啓之編（筆宝義隆 分担執筆）
Total Pages
344
Publisher
化学同人
ISBN
9784759817331
Related Report
