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Analysis of NETs and tumor cell metastasis in animal models of postoperative complications

Research Project

Project/Area Number 19K18040
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionKeio University

Principal Investigator

YAMASHITA Toshiki  慶應義塾大学, 医学部(信濃町), 助教 (10815179)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords炎症 / 腫瘍転移 / NETs / トロンボモジュリン / 転移 / CTC / rTM
Outline of Research at the Start

食道癌をはじめ高度な手術侵襲を伴う消化器系悪性腫瘍疾患では、術後の感染症や合併症に伴う炎症反応が癌細胞の転移に有利な環境を提供しcirculating tumor cells(以下、CTC)による転移・再発の引き金となることが危惧されている。
本研究は、腫瘍細胞の転移環境に血管内皮組織の破綻や好中球細胞外トラップ(Neutrophil extracellular traps; NETs)形成が関与すると仮説を立て、術後合併症や感染症に誘発される癌転移におけるNETsの役割を明らかにする。

Outline of Final Research Achievements

Highly invasive treatments for malignant diseases induce cytokine storms and coagulation abnormalities in the perioperative period. In recent years, neutrophil extracellular traps (NETs) are formed by crosstalk between inflammation and coagulation, and are suggested that they are involved in tumor development. In this study, the relationship between inflammation-induced NETs formation and tumor cell metastasis was examined using a mouse hematogenous lung metastasis model. It was suggested that inflammation promotes lung metastasis. And the effect of suppressing lung metastasis by administration of human recombinant thrombomodulin (rTM) was examined. It was suggested that administration of rTM may suppress NETs formation and lung metastasis.

Academic Significance and Societal Importance of the Research Achievements

本研究では、高度の炎症によって形成されるneutrophil extracellular traps (NETs)および肺転移が亢進する可能性が示唆された。さらにトロンボモジュリン(rTM)投与によってNETs形成および肺転移が抑制されている可能性が示唆された。以上より、NETs形成と転移は密接に関わっている可能性があり、更なる機序の解明が今後の治療戦略の改善につながっていく可能性が示唆された。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2022-01-27  

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