Analysis of the role of cancer cell-derived exosomes in peritoneal dissemination

• Project/Area Number: 18K16351
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Ikuta Daiji 滋賀医科大学, 医学部, 客員助教 (00581935)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 腹膜播種 / エクソソーム / 大腸癌 / Exosome

Outline of Final Research Achievements

In this study, we investigated the effect of cancer-derived exosomes on peritoneal dissemination using CT26 cells, a murine colon cancer cell line. Exosomes were collected from the CT26 cell line by ultracentrifugation. When exosomes were administered for 3 weeks, referring to a previous paper on hematogenous metastasis, exosomes inhibited the formation of peritoneal dissemination. The same was observed in nude mice, suggesting that the intraperitoneal administration of cancer cell-derived exosomes inhibits the formation of peritoneal dissemination. Histological examination after intraperitoneal administration of exosomes alone showed no increase in peritoneal fibrosis or angiogenesis, suggesting that exosomes may not increase fibrosis in the peritoneal cavity.

Academic Significance and Societal Importance of the Research Achievements

癌細胞由来のエクソソームは、癌の血行性転移に関与していることが最近報告されている。一方で、血行性転移とは異なる転移形態である腹膜播種に関しても、 卵巣癌においてエクソソームの関連を示唆する報告はあるが、消化器癌においてその関与は不明である。本研究では癌由来エクソソームが大腸癌においても腹膜播種に影響を及ぼす可能性を示唆しており、今後の腹膜播種のメカニズムの解明に寄与する可能性がある。