Analysis of interraction of multiple myeloma cells and bone marrow stroma cells using xenograft models
| Project/Area Number |
17H03572
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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 |
Laboratory animal science
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| Research Institution | Tokai University |
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Principal Investigator |
ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014)
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| Co-Investigator(Kenkyū-buntansha) |
八幡 崇 東海大学, 医学部, 准教授 (10398753)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | ニッチ / 多発性骨髄腫 / インタラクトーム / ヒト環境マウス / ニッチ間相互作用 / 人環境マウス |
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| Outline of Final Research Achievements |
We demonstrated for the first time that niche-induced Jagged1-Notch signaling activates PKC, subsequently phosphorylates MARCKS, and finally leads to the proliferation, survival and acquired resistance to bortezomib in multiple myeloma cells. as a molecular mechanism of Notch signaling activation through cancer niche. In addition, in order to analyze the interactions that occur specifically between multiple myeloma cells and niches, we performed an interactome analysis using xenograft models and identified nine interactions that may be involved in bortezomib resistance. The effect of SEMA3A-NRP1 on bortezomib susceptibility among the candidates is currently being analyzed in multiple myeloma cells and bone marrow stroma cells.
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| Academic Significance and Societal Importance of the Research Achievements |
多発性骨髄腫の薬剤耐性メカニズムの中で重要な要素としてがん―ニッチ相互作用が深く関わっていることが分かっているが、in vivoにおいてがんとニッチを同時に解析する適切なツールが欠如している。申請者らが確立したヒト骨髄腫細胞を免疫不全マウスに移植した異種移植マウスを用いて網羅的にインタラクトーム解析を行うことで、薬剤耐性に関与する相互作用のメカニズムの全貌が明らかにあると考えられ、最終的にはニッチを標的とする新たな治療薬の開発を通して多発性骨髄腫の治癒につながる重要な治療オプションにつながる可能性がある。
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Jak-Stat pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications2020
Author(s)
Ogiya D, Liu J, Ohguchi H, Kurata K, Samur M, Yai YT, Adamia S, Ando K, Hideshima T, Anderson K.
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Journal Title
Blood,
Volume: 136
Issue: 20
Pages: 2234-2345
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial.2018
Author(s)
Watanabe T, Tobinai K, Wakabayashi M, Morishima Y, Kobayashi H, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Yoshino T, Nawano S, Terauchi T, Hotta T, Nagai H, Tsukasaki K; JCOG0203 Collaborators（Yamauchi T et al.）.
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Journal Title
Lancet Haematol
Volume: 5
Issue: 11
Pages: 520-531
DOI
Related Report
Peer Reviewed / Open Access
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