Development of a novel therapeutic modality against both cancerous and inflammatory diseases based on the understanding of the characteristics of mesothelial cells
| Project/Area Number |
17K19628
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
Sekido Yoshitaka 愛知県がんセンター(研究所), 分子腫瘍学分野, 副所長兼分野長 (00311712)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 龍洋 愛知県がんセンター(研究所), 分子腫瘍学分野, 主任研究員 (70547893)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 中皮細胞 / 細胞増殖 / 上皮間葉転換 / アノイキス / 3次元培養 / シグナル伝達系 / 遺伝子発現 / 細胞特性 / 癌 / 中皮 / 炎症 / 分子標的 |
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| Outline of Final Research Achievements |
Mesothelial cells show different cellular characteristics comparing to epithelial cells. Mesothelial cells play important roles on cancer and inflammation, but the study of mesothelial cells is lagging behind. In this study, we focused on anoikis resistance and epithelial-to-mesenchymal transition. We employed several immortalized mesothelial cell lines which we established and performed comprehensive mRNA expression analysis, phospho-receptor tyrosine kinase array, and three dimensional culture. We found that the immortalized mesothelial cells with epithelial morphology showed a characteristic gene expression profile, phosphorylation status of the receptor tyrosine kinases, and sensitivity to anoikis. We also obtained unique findings of these immortalized mesothelial cell lines. These results strongly indicated that a new therapeutic strategy might be developed toward diseases which are associated with activated mesothelial cells.
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| Academic Significance and Societal Importance of the Research Achievements |
中皮細胞は胸膜・腹膜の表面を覆い、主に臓器間の潤滑な移動・摩擦の軽減といった役割を担う。しかし、中皮細胞は他にも様々な役割を有することが明らかとなり、活性化した中皮細胞はがんや炎症の主座や支持組織として、病態の悪性化や重症化に結び付くことが示唆されている。一方、中皮細胞の研究は極めて遅れており、その本態についてはほとんど明らかになっていない。本研究成果により、中皮細胞のアノイキス抵抗性や上皮間葉転換に関してその特性の一端が明らかとなった。本研究を今後さらに継続・発展させることにより、中皮細胞の増殖・活性化が基盤となる疾患の新規治療法の開発に応用可能であることが強く示唆された。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Connective tissue growth factor-specific monoclonal antibody inhibits growth of malignant mesothelioma in an orthotopic mouse model.2018
Author(s)
Ohara Y, Chew SH, Misawa N, Wang S, Somiya D, Nakamura K, Kajiyama H, Kikkawa F, Tsuyuki Y, Jiang L, Yamashita K, Sekido Y, Lipson KE, Toyokuni S.
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Journal Title
Oncotarget
Volume: 9
Issue: 26
Pages: 18494-18509
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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