2017 Fiscal Year Final Research Report
A new therapeutic strategy for multiple myeloma by targeting senescence of bone marrow microenvironment
| Project/Area Number |
15K09465
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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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| Research Field |
Hematology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | リゾホスファチジン酸 / 間葉系幹細胞 / 多発性骨髄腫 / 細胞老化 |
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| Outline of Final Research Achievements |
It has widely been known that mutual crosstalk between myeloma cells and mesenchymal stromal cells (MSCs) in bone marrow is important for progression of multiple myeloma. In this study, we clearly demonstrated that lysophosphatidic acid (LPA), a kind of lipid mediators, drastically changes phenotypes of MSCs, namely, myeloma-supportive or myeloma-suppressive. From the results by gene silencing of MSCs using siRNA, signaling via LPA receptor subtype 1 (LPA1) and 3 (LPA3) modulates cellular senescence of MSCs positively and negatively, respectively, and also regulated proliferation of myeloma cells positively and negatively, respectively. This study produced clear evidence toward etiology of multiple myeloma that its incidence rate and severity proportionally increase with aging.
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| Free Research Field |
血液内科学
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