2019 Fiscal Year Final Research Report
Elucidation of interaction between lymphoma cells and tumor microenvironment involved in organ tropism and development of novel therapies
| Project/Area Number |
17K09922
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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 | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 悪性リンパ腫 / 微小環境 / 腫瘍関連線維芽細胞 / 臓器指向性 |
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| Outline of Final Research Achievements |
In this study, we elucidated that cancer associated fibroblasts (CAFs) derived from nodal lesion of malignant lymphoma enhanced glucose metabolism in lymphoma cells leading to those survival through the secretion of pyruvate and exosomes from CAFs. We also elucidated that emetine, approved as an emetic and anti-protozoal drug, demonstrated a therapeutic effect on intractable B-cell lymphoma cells through the inhibition of glucose metabolism. Moreover, we elucidated that exosomes were involved in a susceptibility to anti-pyrimidine drug through the modulation of its transporter. In terms of extranodal lesion of malignant lymphoma, we identified a gene that is specifically expressed in the central nervous system (CNS) lesions and demonstrated that the gene is involved in those formation.
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| Free Research Field |
血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
悪性リンパ腫の節性病変におけるCAFについては、知見がそれほど集積しておらず、CAFより分泌されるピルビン酸およびエクソソームが、腫瘍細胞への生存に関与していることを明らかにしたことには学術的意義があると考えられる。さらに本研究では、エクソソームが、抗ピリミジン薬の膜輸送タンパクの発現変化を通して、その感受性に関与し、実際の臨床検体においても、膜輸送タンパク発現が抗ピリミジン薬の感受性予測因子となり得ることを示した。抗ピリミジン薬は、悪性リンパ腫診療における救援療法のキードラッグの一つであり、膜輸送タンパク発現を評価することにより、実際の診療における適切な治療選択に有用となる可能性がある。
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