The role of TFF1 to inhibit the development of pancreatic cancer

• Project/Area Number: 17K10695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: Yamaguchi Junpei 名古屋大学, 医学部附属病院, 助教 (00566987)
• Co-Investigator(Kenkyū-buntansha): 梛野 正人 名古屋大学, 医学系研究科, 教授 (20237564) ; 國料 俊男 名古屋大学, 医学部附属病院, 講師 (60378023) ; 横山 幸浩 名古屋大学, 医学系研究科, 寄附講座教授 (80378091)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膵癌 / TFF1 / 前癌病変 / TFF / 癌

Outline of Final Research Achievements

Trefoil Factor Family 1 is the secreted protein and supposed to be the tumor suppressor in gastric carcinogenesis. We analyzed surgically-resected pancreatic specimen, pancreatic cancer cell line and genetically-engeneered mouse model to investigate the association of TFF1 and pancreatic carcinogenesis. This study revealed that TFF1 inhibits malignant transformation of pancreatic premelignant lesions by controling epithelial-mesenchymal transition (EMT). TFF1 has the potential to be the novel therapeutic strategy for pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

膵癌は難治性の悪性疾患であり、患者全体の5年生存率は約5％と推定されている。膵癌患者の予後が不良な原因は、多くの患者が切除不能な状態で発見されることに加え、たとえ治癒切除が施行されたとしても術後の再発が多い事による。膵癌の予後を改善するためには再発進行膵癌に対する新たな治療戦略の開発が必須であるだけでなく、高リスク患者における膵癌発生を予防する事が重要である。本研究でTFF1は膵癌の浸潤および転移を抑制する作用があることが判明した。TFF1を用いた新規治療方法の開発は、進行再発膵癌に対する治療戦略になるのみならず膵癌発生予防にも有用である可能性がある。

Research Products

• [Journal Article] Trefoil Factor 1 inhibits epithelial-mesenchymal transition of pancreatic intraepithelial neoplasm. (2018)
  • Author(s): Yamaguchi J, Yokoyama Y, Kokuryo T, Ebata T, Enomoto A, Nagino M.
  • Journal Title: Journal of Clinical Investigation Volume: 128(8) Issue: 8 Pages: 3619-3629
  • DOI: 10.1172/jci97755
  • Peer Reviewed / Open Access
• [Journal Article] Trefoil factor family 1 expression in the invasion front is a poor prognostic factor associated with lymph node metastasis in pancreatic cancer (2017)
  • Author(s): Masaki Sunagawa, Junpei Yamaguchi, Toshio Kokuryo, Tomoki Ebata, Yukihiro Yokoyama, Gen Sugawara, Masato Nagino
  • Journal Title: Pancreatology Volume: 17 (5) Issue: 5 Pages: 782-787
  • DOI: 10.1016/j.pan.2017.07.188
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Trefoil Factor Family 1 (TFF1) Inhibits Epithelial-mesenchymal Transition and Enhances the Chemosensitivity of Pancreatic Ductal Adenocarcinoma (PDAC) (2019)
  • Author(s): J Yamaguchi, T Kokuryo, Y Yokoyama, T Ebata, and M Nagino
  • Organizer: APA annual meeting
  • Int'l Joint Research
• [Presentation] Trefoil Factor 1 inhibits epithelial-mesenchymal transition (EMT) of pancreatic intraepithelial neoplasm. (2018)
  • Author(s): Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo and Masato Nagino
  • Organizer: AACR Pancreatic cancer: advances in science and clinical care
  • Int'l Joint Research
• [Presentation] Preserved expression of TFF1 in invasive front is a poor prognostic factor in PDAC (2017)
  • Author(s): Junpei Yamaguchi, Masaki Sunagawa, Yukihiro yokoyama, Toshio Kokuryo, Tomoki Ebata, Masato Nagino
  • Organizer: Joint Congress of The 6th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association & The 29th Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
  • Int'l Joint Research
• [Presentation] 遺伝子改変マウスを用いたTFF1欠損による膵浸潤癌発生に関する検討 (2017)
  • Author(s): 山口淳平、江畑智希、横山幸浩、國料俊男、梛野正人
  • Organizer: 第48回日本膵臓学会大会