| Project/Area Number |
17K08706
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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 |
Human pathology
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| Research Institution | Nagoya City University (2019-2020)
Aichi Medical University (2017-2018) |
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Principal Investigator |
Inaguma Shingo 名古屋市立大学, 医薬学総合研究院(医学), 実験病態病理学教授 (80410786)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | CD274 / 膵臓癌 / 大腸癌 / CD70 / 癌間質 / 浸潤 / 細胞増殖 / PD-L1 / 悪性形質 / ヘッジホッグ |
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| Outline of Final Research Achievements |
This study identified that PD-L1-high fraction of pancreatic and colorectal cancer cells harbor higher potentials for migration, invasion, and cellular proliferation than PD-L1-low fraction. Gene expression microarray analyses identified specifically expressed genes in PD-L1-high fraction. Among them, we have selected several genes those might be responsible for tumor stemness and epithelial-mesenchymal transition (EMT). We are now analyzing the malignant potentials of pancreatic and colorectal cancer cells those gene expressions were modulated by lentiviral vectors.
This study also identified the clinicopathological characteristics of PD-L1-positive colorectal cancer from tissue microarray analyses. Furthermore, prognostic significance of CD47, PHH3, and PBK expressions in colorectal cancer cells were identified. Also, CD70 expression in tumor-associated fibroblasts was identified as a worse prognostic factor in colorectal cancer patients.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、様々な固形腫瘍において、PD-1/PD-L1シグナルを標的とした分子標的治療薬が用いられているものの、単剤では腫瘍の治癒には至っておらず、他の分子標的治療薬との併用療法の重要性が示唆されている。本研究において、膵臓癌、および大腸癌におけるPD-L1高発現分画が高い悪性度を有していること、また、その分画において特異的に発現する遺伝子群を同定したことで、それらの遺伝子が新規併用療法の標的となる可能性を有していると考えられた。
また、腫瘍組織アレイを用いた発現解析より同定された予後因子群に関しても、今後、それらの分子メカニズムを解析することで、新たな治療標的となりうると考えている。
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