Elucidating mechanisms for metastasis and recurrence through a tumor cell dormancy model
| Project/Area Number |
19K10360
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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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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Shinriki Satoru 熊本大学, 大学院生命科学研究部(医), 准教授 (00583048)
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| Co-Investigator(Kenkyū-buntansha) |
松井 啓隆 熊本大学, 大学院生命科学研究部(医), 教授 (60379849)
植田 光晴 熊本大学, 病院, 教授 (60452885)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 循環腫瘍細胞 / 転移 / メカノバイオロジー / 転移・再発 / 休眠播種癌細胞 / 静止期癌細胞 |
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| Outline of Research at the Start |
癌による死亡のほとんどは転移・再発を原因とする。分裂停止状態で潜んでいる癌細胞が増殖を再開することで致死的な転移・再発に至ると考えられているため、静止期癌細胞の性質解明とその制御が癌治療において重要である。本研究では、申請者が開発しつつある静止期癌細胞を模倣するモデルを用いて、転移・再発メカニズムの解析を行うことで、新たな癌治療法の開発を目指す。
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| Outline of Final Research Achievements |
Tumor cells disseminated from the primary tumor as circulating tumor cells (CTCs) settle into distant organs, after which they effectively remain dormant until a trigger, as yet unknown, rouses them. We applied high-resolution DNA barcode tracking to a mouse model that recapitulated the metastatic dormancy of head and neck squamous cell carcinoma. We identified specific subclonal population that preferentially generated functionally homotypic CTC clusters adaptive to fluid shear stress and dominated distant organs. Then, we proposed a novel clonal selection model during metastasis in which metastatic cells are selected based on their intrinsic mechano-sensitivity.
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| Academic Significance and Societal Importance of the Research Achievements |
癌による死亡のほとんどは転移再発を原因とする。癌細胞は血中に侵入すると、循環腫瘍細胞（CTC）として遠隔臓器に播種・生着する。本研究では、高い転移能を持つことが知られている、複数の癌細胞が凝集したCTC（CTCクラスター）を構成する細胞の特性の一端を明らかとした。そして、癌細胞自身の機械的力に対する応答能の違いが、転移過程で起こる癌細胞の選択に寄与しているという、新たなクローン選択機構を提唱した。今後、この新たなクローン選択機構を支える分子基盤を解明することは、癌の病態解明や新たな診断・治療法の開発に寄与すると考えられる。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Colonization of distant organs by tumor cells generating circulating homotypic clusters adaptive to fluid shear stress2021
Author(s)
Maeshiro M, Shinriki S, Liu R, Nakachi Y, Komohara Y, Fujiwara Y, Ohtsubo K, Yoshida R, Iwamoto K, Nakayama H, Matsui H.
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Journal Title
Sci Rep
Volume: 11
Issue: 1
Pages: 6150-6150
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel dot-blot assay for detection of vascular Notch3 aggregates in patients with CADASIL2020
Author(s)
Ma Y, Ueda M, Ueda A, Shinriki S, Nagatoshi A, Isoguchi A, Okada M, Tasaki M, Nomura T, Inoue Y, Masuda T, Misumi Y, Yamashita T, Matsui H, Ando Y.
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Journal Title
J Neurol Sci
Volume: 415
Pages: 116931-116931
DOI
Related Report
Peer Reviewed
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[Journal Article] Evaluation of an amplicon-based custom gene panel for the diagnosis of hereditary tumors.2020
Author(s)
Shinriki S, Maeshiro M, Shimamura K, Kawashima J, Araki E, Ibusuki M, Yamamoto Y, Iwase H, Miyamoto Y, Baba H, Yamaguchi M, Matsui H.
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Journal Title
Neoplasma
Volume: －
Issue: 04
Pages: 898-908
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Loss of tumor suppressor CYLD expression triggers cisplatin resistance in oral squamous cell carcinoma.2019
Author(s)
Suenaga N, Kuramitsu M, Komure K, Kanemaru A, Takano K, Ozeki K, Nishimura Y, Yoshida R, Nakayama H, Shinriki S, Saito H, Jono H.
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Journal Title
J Mol Sci
Volume: 20
Issue: 20
Pages: 5194-5194
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CT texture analysis for the prediction of KRAS mutation status in colorectal cancer via a machine learning approach.2019
Author(s)
Taguchi N, Oda S, Yokota Y, Yamamura S, Imuta M, Tsuchigame T, Nagayama Y, Kidoh M, Nakaura T, Shiraishi S, Funama Y, Shinriki S, Miyamoto Y, Baba H, Yamashita Y.
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Journal Title
Eur J Radiol
Volume: 118
Pages: 38-43
DOI
Related Report
Peer Reviewed
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