Exploring novel mechanisms of chemotherapy-induced metastasis
Project/Area Number |
19K07659
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | Kansai Medical University (2021-2022) Kanazawa University (2020) The University of Tokyo (2019) |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 転移 / 化学療法 / がん |
Outline of Research at the Start |
近年、抗がん剤投与によりむしろ転移が促進される「化学療法誘導性転移」という概念が提唱され、抗がん剤の治療効果を下げる一因として着目されていが、そのメカニズムの詳細は不明である。そこで本研究では抗がん剤の治療ポテンシャルを最大化するための分子基盤の創造と化学療法誘導性転移の予防法の確立を目指す。
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Outline of Final Research Achievements |
It has been reported that chemotherapy using cytotoxic anticancer agents may rather promote cancer metastasis, but the detailed mechanism is unknown. In this study, we focused on the molecule Mint3, which is known to promote cancer metastasis in macrophages, and analyzed chemotherapy-induced metastasis using Mint3-deficient mice. The results showed that chemotherapy-induced metastasis was suppressed in Mint3-deficient mice. Further analysis revealed that chemotherapy-induced metastasis is induced by Mint3-dependent induction of Molecule X expression in alveolar type II epithelial cells by chemotherapy-activated macrophages, and that Molecule X promotes cancer cell metastasis.
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、詳細が不明であった化学療法誘導性転移の分子メカニズムの一端が明らかとなった。特に、マクロファージ―肺胞II型上皮細胞―がん細胞の細胞間相互作用が、肺への化学療法誘導性転移に関わることは、臓器特異性をもった化学療法誘導性転移機構があることを解明した点で学術的に重要な発見である。また、Mint3や分子Xを阻害することで化学療法誘導性転移が抑制されることから、術前化学療法時にこれら分子の阻害剤を併用することで、化学療法誘導性転移のリスクを下げる可能性があるため、今後の臨床応用に向けて社会的意義のある研究成果である。
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Report
(5 results)
Research Products
(56 results)
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[Journal Article] Spatial and single-cell transcriptomics decipher the cellular environment containing HLA-G+ cancer cells and SPP1+ macrophages in colorectal cancer.2023
Author(s)
Ozato Y, Kojima Y, Kobayashi Y, Hisamatsu Y, Toshima T, Yonemura Y, Masuda T, Kagawa K, Goto Y, Utou M, Fukunaga M,... Mimori K.
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Journal Title
Cell Rep
Volume: 42(1)
Issue: 1
Pages: 111929-111929
DOI
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Peer Reviewed / Open Access
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[Journal Article] Trans-homophilic interaction of CADM1 promotes organ infiltration of T-cell lymphoma by adhesion to vascular endothelium.2022
Author(s)
Kasai Y, Gan SP, Funaki T, Ohashi-Kumagai Y, Tominaga M, Shiu S-J, Suzuki D, Matsubara D, Sakamoto T, Sakurai-Yageta M, Ito T, Murakami Y.
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Journal Title
Cancer Science
Volume: in press
Issue: 5
Pages: 1-2
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pharmacological inhibition of Mint3 attenuates tumour growth, metastasis, and endotoxic shock2021
Author(s)
Takeharu Sakamoto, Yuya Fukui, Yasumitsu Kondoh, Kaori Honda, Takeshi Shimizu, Toshiro Hara, Tetsuro Hayashi, Yurika Saitoh, Yoshinori Murakami, Jun-Ichiro Inoue, Shuichi Kaneko, Hiroyuki Osada, Motoharu Seiki
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Journal Title
Communications Biology
Volume: 4
Issue: 1
Pages: 1165-1165
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TGF-β-dependent reprogramming of amino acid metabolism induces epithelial?mesenchymal transition in non-small cell lung cancers2021
Author(s)
Nakasuka Fumie, Tabata Sho, Sakamoto Takeharu, Hirayama Akiyoshi, Ebi Hiromichi, Yamada Tadaaki, Umetsu Ko, Ohishi Maki, Ueno Ayano, Goto Hisatsugu, Sugimoto Masahiro, Nishioka Yasuhiko, Yamada Yasuhiro, Tomita Masaru, Sasaki Atsuo T, Yano Seiji, Soga Tomoyoshi
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Journal Title
Communications Biology
Volume: 4
Issue: 1
Pages: 1-12
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells.2020
Author(s)
Yoshino S, Matsui Y, Fukui Y, Seki M, Yamaguchi K, Kanamori A, Saitoh Y, Shimamura T, Suzuki Y, Furukawa Y, Kaneko S, Seiki M, Murakami Y, Inoue JI, Sakamoto T.
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Journal Title
Sci Rep
Volume: 10
Issue: 1
Pages: 9275-9275
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Mint3-FIH-1相互作用の薬理的阻害は腫瘍の増殖、転移、エンドトキシンショックを減弱させる2021
Author(s)
坂本毅治, 福井 優也, 近藤 恭光 , 本田 香織 ,清水 猛, 原 敏朗 , 林 哲郎, 齊藤 百合花, 村上 善則, 井上 純一郎, 金子 周一, 長田 裕之, 清木 元治.
Organizer
第44回日本分子生物学会年会
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