2020 Fiscal Year Final Research Report
The Role of Neutrophil Extracellular Traps (NETs) in Cancer Metastasis
Project/Area Number |
18K16302
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kanazawa University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Keywords | 好中球細胞外トラップ / 血小板凝集 / 腹腔内感染症 / 膵癌 / がん転移 |
Outline of Final Research Achievements |
The impacts of postoperative abdominal infectious complications increase hematogenous distant metastasis and result in poor long term survival after curative resection. Even if curative resection can be performed, the presence of circulating tumor cells is affected. The liver, the most common site of metastases, is an important organ in innate immune surveillance. The purpose of this study was to identify the effect of platelets on escape from innate immune surveillance in postoperative abdominal infectious complications. In the infectious model, although epithelial cells without platelet adhesion were in an apoptotic state, mesenchymal cells showed many viable cancer cells surrounded by activated platelets. Mesenchymal cells could escape from immune surveillance by becoming surrounded by adhered activated platelets. We hypothesized that this mechanism would be the first step in cancer metastasis formation.
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Free Research Field |
消化器癌
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Academic Significance and Societal Importance of the Research Achievements |
これまで NETsの機能として血栓形成や、自己免疫性疾患である全身性エリテマトーデ ス(SLE)の発症に重要な働きをしていることが報告されてきた。癌転移形成における働きに関しても報告があるが、NETs形成と血小板凝集による機能解析に関しては、十分に解明されていない。 本研究により癌転移形成においてNETs形成・血小板凝集が関与する病態が解明できたため、今後抗血小板作用を有する薬剤の新規作用効果としての発展的な実験を行うことができる。現在PDE3阻害剤(cilostazol)を用いて検討を行っているが、既に抗血小板薬として臨床で使用されており、今後臨床応用も比較的容易に図ることができると考える。
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