Neutrophil extracellular traps in the development of peritoneal metastasis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10606
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Jichi Medical University
• Principal Investigator: Hosoya Yoshinori 自治医科大学, 医学部, 教授 (30275698)
• Co-Investigator(Kenkyū-buntansha): 北山 丈二 自治医科大学, 医学部, 教授 (20251308) ; 山口 博紀 自治医科大学, 医学部, 教授 (20376445) ; 大澤 英之 自治医科大学, 医学部, 講師 (60458271) ; 倉科 憲太郎 自治医科大学, 医学部, 講師 (70382900)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 好中球細胞外トラップ / 腹膜播種 / 胃癌 / 接着 / DNAse 1 / 低比重好中球

Outline of Final Research Achievements

The number of CD66b (+) low density neutrophils (LDN) with mature phenotype was markedly elevated in postoperative as compared with preoperative lavages in patients who underwent laparotomy due to gastric cancer. Short term culture of the purified LDN produced many threadlike structures positive for SYTOX, suggesting the NETs formation. Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached on the NETs, which was abolished by DNAse I. Intraperitoneal co-transfer of the LDN with MKN45 in nude mice strongly augments the metastasis formation on peritoneum, which was strongly suppressed by the following IP administration of DNAse I. Many NETs-like structures were detected on the surface of human omental tissue resected by gastrectomy. NETs on peritoneal surface can assist the clustering and growth of free tumor cells disseminated in abdomen. Disruption of the NETs by DNAse might be useful to prevent the peritoneal recurrence after abdominal surgery.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

腹膜播種の成立における腹腔内滲出好中球とNETｓの役割を明らかにすると共に、DNAse1投与によるNETｓの分解が播種再発の予防につながる可能性があることを見出した。今後の腹膜播種治療における新たな方法論を導く糸口になる成果を得た。