Elucidation of mechanisms of cancer progression by exosome derived from hematopoietic cells

• Project/Area Number: 17K10601
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Yamanashi
• Principal Investigator: ICHIKAWA Daisuke 山梨大学, 大学院総合研究部, 教授 (20347446)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 消化器癌 / exosome / 血球細胞 / 細胞間情報伝達 / 癌 / 遺伝子 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Uptake of red blood cell- (RBC) and platelet-derived exosomes into gastric cancer and mesothelial cell lines were confirmed. Increased migration ability was confirmed in cell lines with addition of the RBC-derived exosomes compared with control. Similarly, addition of platelet-derived exosomes resulted in increase of migration ability of gastric cancer cell lines. Further PCR-array based analysis demonstrated that addition of the platelet-derived exosomes generated alteration in some gene expressions in gastric cancer cell lines. On the other hand, co-culture of gastric cancer cell lines with platelet generated adherence of platelet to cancer cells, and the co-culture led increases of proliferation, migration and invasion ability of gastric cancer cell lines.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、無核である血球細胞に含まれる様々な遺伝情報が細胞外に分泌され、それらが受け側細胞に取り込まれることによって、様々な機能変化を来たすことが判明した。実臨床では、担癌状態の末期には様々な血球の異常が認識されており、外科手術においては、術野への多量の血液が暴露することも周知の事実である。これら血球細胞の癌進展への関与についての更なる分子機序の解明によって、全く新たな治療法の開発が期待され、依然、治療成績が不良である高度進行癌患者に対して極めて大きな福音となると考えられる。

Research Products

• [Journal Article] Inhibition of apoptosis by miR-122-5p in alpha-fetoprotein producing gastric cancer. (2019)
  • Author(s): Maruyama S, Furuya S, Shiraishi K, Shimizu H, Saito R, Akaike H, Hosomura N, Kawaguchi Y, Amemiya H, Kawaida H, Sudo M, Inoue S, Kono H, Ichikawa D.
  • Journal Title: Oncology Report Volume: 41 Pages: 2595-2560
  • DOI: 10.3892/or.2019.7023
  • Peer Reviewed
• [Presentation] 胃癌患者での血小板由来microparticleの検討 (2019)
  • Author(s): 丸山 傑，齊藤 亮，芦沢直樹，中山裕子，清水浩紀，市川大輔
  • Organizer: 第78回日本癌学会学術総会