| Project/Area Number |
18K15962
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 悪性胸膜中皮腫 / 腫瘍関連マクロファージ / インフラマソーム / 癌幹細胞 / IL-1受容体 / アスベスト |
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| Outline of Final Research Achievements |
Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive malignant neoplasm. Developing a novel therapeutic strategy has been a pressing issue to bring about a better outcome for MPM. We found that expression of interleukin-1 receptor (IL-1R) was upregulated in MPM cells compared to normal mesothelial cells. Stimulation by pro-inflammatory cytokine IL-1β promoted MPM cells to form spheroids along with upregulating cancer stem cell marker CD26, indicating that IL-1β enhanced the malignant potential of MPM. We also identified tumor-associated macrophages (TAMs) as the major source of IL-1β in MPM microenvironment. Immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with standard chemotherapy revealed that overexpression of IL-1R tended to correlate with poor overall survival. Collectively, interaction between MPM cells and TAMs through IL-1β/IL-1R signal could be a promising candidate as target for novel treatment of MPM.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性胸膜中皮腫（Malignant pleural mesothelioma: MPM）は難治性悪性腫瘍で、「発生」については、アスベストの関与が証明されているが、その「進展」にアスベストが関与しているかは解明されていない。
本研究では、アスベストが腫瘍関連マクロファージのインフラマソームを恒常的に活性化する事によって分泌される炎症性サイトカインIL-1βが、MPM細胞のIL-1Rを介してMPMの悪性度の促進、幹細胞化に関与している事が示唆された。
従って、IL-1β/IL-1Rのシグナルを抑制する事は、化学療法に対するMPM細胞の感受性を高め、予後の改善に繋がる可能性があると考えられた。
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