Immature Schwann cells contribute to pancreatic cancer cell migration and invasion

• Project/Area Number: 18K07382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Osaka University
• Principal Investigator: Suzuki Masami 大阪大学, 医学系研究科, 助教 (80434182)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: がん / シュワン細胞 / がん細胞 / クロストーク

Outline of Final Research Achievements

The nerve repair signaling following nerve injury may facilitates cancer progression. I previously revealed that Schwann cells were dedifferentiated into immature Schwann cells by cancer cells-induced peripheral nerve injury. In this study, I investigated the role of immature Schwann cells in cancer cells migration/invasion. Conditioned medium from immature Schwann cells significantly enhanced the migration of cancer cells toward the conditioned medium. To explore the collaboration between immature Schwann cells and cancer cells, we developed in vitro coculture system. Immature Schwann cells was associated with cancer cells with their protrusions and formed tunnels. These results suggest that immature Schwann cells dedifferentiated by cancer cells might be a key regulator of cancer cell migration and invasion.

Academic Significance and Societal Importance of the Research Achievements

これまでのがん研究は、発生学や免疫学からのアプローチが主で、神経科学的にアプローチされることは少なかった。本研究の学術的意義は、がんにより引き起こされる神経障害、特にシュワン細胞の脱分化により誘導された未分化型のシュワン細胞が、がん細胞の遊走能および浸潤能を増大させることを明らかにした点である。本研究成果は、がんによる神経障害を制御することががんの進展を抑制することを示唆しており、これら重複する分子メカニズムをターゲットとした治療は、神経障害に伴う難治性の痛みを軽減するだけではなく、がんの増悪を抑制できる可能性が考えられる。

Research Products

• [Journal Article] E74-Like Factor 3 Is a Key Regulator of Epithelial Integrity and Immune Response Genes in Biliary Tract Cancer (2020)
  • Author(s): Suzuki Masami、Saito-Adachi Mihoko、Arai Yasuhito、Fujiwara Yuko、Takai Erina、Shibata Shinsuke、Seki Masahide、Rokutan Hirofumi、Maeda Daichi、Horie Masafumi、Suzuki Yutaka、Shibata Tatsuhiro、Kiyono Tohru、Yachida Shinichi
  • Journal Title: Cancer Research Volume: 81 Issue: 2 Pages: 489-500
  • DOI: 10.1158/0008-5472.can-19-2988
  • Peer Reviewed / Open Access
• [Journal Article] Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 Through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways (2019)
  • Author(s): Miyano K, Shiraishi S, Minami K, Sudo Y, Suzuki M, Yokoyama T, Terawaki K, Nonaka M, Murata H, Higami Y, Uezono Y.
  • Journal Title: Int J Mol Sci Volume: 13 Pages: 3271-3271
  • Peer Reviewed
• [Journal Article] Establishment of preclinical chemotherapy models for gastroenteropancreatic neuroendocrine carcinoma (2018)
  • Author(s): Ohmoto A, Suzuki M, Takai E, Routan H, Fujiwara Y, Morizane C, Yanagihara K, Shibata T, Yachida S
  • Journal Title: Oncotarget Volume: 30 Issue: 30 Pages: 21086-21099
  • DOI: 10.18632/oncotarget.24930
  • Peer Reviewed / Open Access