Elucidation of the mechanism of cancer pathology caused by disruption of immune regulation through TFL deficit

• Project/Area Number: 18K08356
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kobe University
• Principal Investigator: Kentaro Minagawa 神戸大学, 医学研究科, 医学研究員 (80432574)
• Co-Investigator(Kenkyū-buntansha): 若橋 香奈子 神戸大学, 医学研究科, 医学研究員 (40817178)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: TFL / ZC3H12D / Regnase4 / CXCL13 / Cahexia / RNA regulation / Lymphoma / Bcl2 / Zc3h12d / Regnase / 転写後調節 / リンパ腫

Outline of Final Research Achievements

RNA regulatory molecule TFL is discovered in a chromosomal aberration in lymphomas, and TFL-/- mice are created. TFL-/- mice were bred to lymphoma model mice to investigate the relationship between TFL-/-. Cachexia due to enhanced inflammation was observed in the TFL-deficient mice. We also observed an increase in the chemokine CXCL-13 and a significant decrease in their body weight in correlation with the time of tumor onset. The results showed a trend toward a better prognosis in the TFL-deficient group. In the future, we will reexamine immunostaining and expand the target to other lymphomas.

Academic Significance and Societal Importance of the Research Achievements

TFLは免疫調節という重要な分野ににも関わらずあまり研究されて来なかった。近年、少しづつTFLに関わる報告が増えてきており、いずれも免疫、腫瘍の分野で重要な働きをしていることを示唆するものである。今回我々はマウスのデータを論文発表において、TFLが免疫調節を制御しながら腫瘍のあるマウスの体重減少に関与したことを示した。今後、ますますこの分子の研究が盛んになっていくものと思われる。近い将来TFLが何らかの腫瘍、自己免疫疾患のマーカーとして用いられると考えられる。

Research Products

• [Presentation] TFL Deletion Induces Incredible CXCL13 Secretion and Cachexia in Vavp-Bcl2 Transgenic Mice (2019)
  • Author(s): Yoshio Katayama, Kentaro Minagawa, Kanako Wakahashi, Chie Fukui, Shinichiro Nishikawa, Noboru Asada, Yuko Kawano, Hiroki Kawano, Tomohide Suzuki, Shinichi Ishii, and Toshimitsu Matsui
  • Organizer: The 10th JSH International Symposium 2019
  • Int'l Joint Research
• [Presentation] TFL Deletion Induces Incredible CXCL13 Secretion and Cachexia in Vavp-Bcl2 Transgenic Mice (2018)
  • Author(s): Kentaro Minagawa, Kanako Wakahashi, Chie Fukui, Shinichiro Nishikawa, Noboru Asada, Yuko Kawano, Hiroki Kawano, Tomohide Suzuki, Shinichi Ishii,, Yoshio Katayama, and Toshimitsu Matsui,
  • Organizer: American Society of Hematology
  • Int'l Joint Research