Functional analysis of Crk and Exosome in determining the metastatic organ of cancer
Project/Area Number |
18K07059
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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 49030:Experimental pathology-related
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Research Institution | Hokkaido University |
Principal Investigator |
Tsuda Masumi 北海道大学, 医学研究院, 准教授 (30431307)
|
Co-Investigator(Kenkyū-buntansha) |
田中 伸哉 北海道大学, 医学研究院, 教授 (70261287)
王 磊 北海道大学, 医学研究院, 助教 (70637975)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | がん / 転移 / エクソソーム / Crk / ErbB2 / アダプター分子 / CRK / 癌 / ヘテロジェナイティー |
Outline of Final Research Achievements |
According to this study, it has shown that the adapter molecule Crk controls the kinds and amount of inclusion molecules in exosomes. The exosomes derived from Crk-expressing bladder cancer cells contain ErbB2 together with Crk, and acts on the vascular endothelial cell of the lung of the metastatic organ, which contributes to the development of the lung metastasis of bladder cancer cells. This suggests that Crk and ErbB2 contained in exosomes activate the signal transduction pathway of recipient cells of the metastatic organ and change their characteristics. Many cancers with high expression of Crk have been reported, which suggests that heterogenity is also created for exosome inclusion molecules, which may contribute to the selection and establishment of cancer metastasis.
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、アダプター分子Crkはがん細胞の悪性形質のみならず、エクソソームを介してがんの転移先臓器の再構築と転移形成にも関与することが明らかとなった。これは、アダプター分子がエクソソームを介して転移先臓器の組織環境を整備し、がん転移の成立と促進に寄与することを示す画期的なデータである。現在、Crkとシグナル下流分子C3Gの結合を阻害する薬剤を開発検討中であり、エクソソームにおける効果を検証後は、がん細胞の増殖のみならずエクソソームを介したがんの浸潤・転移を抑制できる可能性があり、多くのがん患者の生命予後の改善に貢献できることが期待される。
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Report
(4 results)
Research Products
(73 results)
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[Journal Article] Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels2021
Author(s)
Suzuka J, Tsuda M, Wang L, Kohsaka S, Kishida K, Semba S, Sugino H, Aburatani S, Frauenlob M, Kurokawa T, Kojima S, Ueno T, Ohmiya Y, Mano H, Yasuda K, Gong JP, Tanaka S
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Journal Title
Nat Biomed Eng
Volume: -
Issue: 8
Pages: 914-925
DOI
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Peer Reviewed / Open Access
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[Journal Article] Involvement of BMP and Wnt signals leading to EMT in colon adenocarcinoma with heterotopic ossification.2021
Author(s)
Katono N, Tsuda M, Suzuka J, Oda Y, Wang L, Tanei ZI, Tanino M, Ohata T, Nagabuchi E, Ishida Y, Kimura S, Iwanaga T, Tanaka S
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Journal Title
Annals of Clinical and Laboratory Science
Volume: 51
Pages: 3-8
Related Report
Peer Reviewed
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[Journal Article] Role of dimerized C16orf74 in aggressive pancreatic cancer: A novel therapeutic target.2020
Author(s)
Kushibiki T, Nakamura T, Tsuda M, Tsuchikawa T, Hontani K, Inoko K, Takahashi M, Asano T, Okamura K, Murakami S, Kurashima Y, Ebihara Y, Noji T, Nakanishi Y, Tanaka K, Maishi N, Sasaki K, Park W-R, Shichinohe T, Hida K, Tanaka S, Hirano S.
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Journal Title
Mol Cancer Ther
Volume: 19
Issue: 1
Pages: 187-198
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Autopsy findings in the early stage of ALS with `dropped head` syndrome.2019
Author(s)
Tanikawa S, Tanino M, Wang L, Ishikawa M, Miyazaki M, Tsuda M, Orba Y, Sawa H, Matoba K, Nakamura N, Nagashima K, Hall W, Tanaka S.
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Journal Title
Neuropathology
Volume: 39
Issue: 5
Pages: 374-377
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical efficacy and safety of first-line nilotinib therapy and evaluation of the clinical utility of the FRET-based drug sensitivity test.2019
Author(s)
Kondo T, Fujioka M, Fujisawa S, Sato K, Tsuda M, Miyagishima T, Mori A, Iwasaki H, Kakinoki Y, Yamamoto S, Haseyama Y, Ando S, Shindo M, Ota S, Nishio M, Kurosawa M, Ohba Y, Teshima T, on behalf of the North Japan Hematology Study Group (NJHSG).
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Journal Title
International Journal of Hematology
Volume: 110
Issue: 4
Pages: 482-489
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Clinicopathological Analysis of Six Autopsy Cases of Sudden Unexpected Death due to Infectious Aortitis in Patients with Aortic Tears2018
Author(s)
Kato MI, Tanino MA, Miyazaki M, Kimura T, Ishida Y, Wang L, Tsuda M, Nishihara H, Nagashima K, Tanaka S
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Journal Title
Internal Medicine
Volume: 57
Issue: 10
Pages: 1375-1380
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2018-05-15
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pre-treatment evaluation of FRET-based drug sensitivity test for patients with CML treated with dasatinib.2018
Author(s)
Kondo T, Fujioka M, Tsuda M, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Nagashima T, Wakasa K, Fujimoto N, Yamamoto S, Yonezumi M, Saito S, Sato S, Ogawa K, Chou T, Watanabe R, Kato Y, Takahashi S, Okano Y, Yamamoto J, Ohta M, Iijima H, Oba K, Kishino S, Sakamoto J, Ishida Y, Ohba Y, Teshima T.
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Journal Title
Cancer Sci.
Volume: 109
Issue: 7
Pages: 2256-2265
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tough and self-recoverable thin hydrogel membranes for biological applications.2018
Author(s)
Ye YN, Frauenlob M, Wang L, Tsuda M, Sun TL, Cui K, Takahashi R, Zhang HJ, Nakajima T, Nonoyama T, Kurokawa T, Tanaka S, Gong JP.
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Journal Title
Advanced Functional Materials.
Volume: 28
Issue: 31
Pages: 1801489-1801489
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Tumor budding and human chorionic gonadotropin-β expression correlate with unfavorable patient outcome in colorectal carcinoma.2018
Author(s)
Konishi Y, Kawamata F, Nishihara H, Homma S, Kato Y, Tsuda M, Kohsaka S, Einama T, Liu C, Yoshida T, Nagatsu A, Tanino M, Tanaka S, Kawamura H, Kamiyama T, Taketomi A.
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Journal Title
Med Oncol.
Volume: 35
Issue: 7
Pages: 104-104
DOI
NAID
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[Journal Article] “Integrated diagnosis” of pilocytic astrocytoma: Molecular diagnostic procedure for an unusual case.2018
Author(s)
Ishida Y, Tsuda M, Sawamura Y, Fujii K, Murai H, Horiuchi N, Orba Y, Sawa H, Hall WW, Nagashima K, Tanaka S.
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Journal Title
Pathology Int.
Volume: 68
Issue: 12
Pages: 694-699
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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