Elucidation of autophagy function in stromal during pancreatic carcinogenesis process and development of new pancreatic cancer diagnosis or carcinogenesis prevention strategy.

• Project/Area Number: 15K19895
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: EGUCHI Daiki 九州大学, 医学研究院, 共同研究員 (90726390)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オートファジー / 癌間質 / 膵臓癌 / 間質 / 発癌

Outline of Final Research Achievements

Autophagy is involved in the proliferation of pancreatic cancer cells in pancreatic cancer, but reports on the relation between pancreatic stellate cells surrounding pancreatic cancer and autophagy were not reported at the time of this study. Therefore, we aimed to clarify the role of autophagy in pancreatic cancer stroma.
We showed that autophagy of pancreatic stellate cells surrounding pancreatic cancer is activated by immunostaining of human pancreatic cancer section. We also showed that autophagy suppression of pancreatic stellate cells reduces invasive ability of pancreatic cancer cells in vitro and in vivo. Furthermore, we showed that pancreatic stellate cells are activated by enhancing autophagy in normal pancreatic stellate cells. We reported to domestic and international academic societies and English journals.

Research Products

• [Journal Article] Autophagy is required for activation of pancreatic sstellate cells, associated with pancreatic cancer progression and promotes growth of pancreatic tumors in mice. (2017)
  • Author(s): Endo S, Nakata K, Ohuchida K, Takesue S, Nakayama H, Abe T, Koikawa K, Okumura T, Sada M, Horioka K, Zheng B, Mizuuchi Y, Iwamoto C, Murata M, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
  • Journal Title: Gastroenterology Volume: 印刷中 Issue: 6 Pages: 1492-1506
  • DOI: 10.1053/j.gastro.2017.01.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility (2016)
  • Author(s): Sada M, Ohuchida K, Horioka K, Okumura T, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M
  • Journal Title: Cancer Lett. Volume: 372 Issue: 2 Pages: 210-218
  • DOI: 10.1016/j.canlet.2016.01.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer (2016)
  • Author(s): Horioka K, Ohuchida K, Sada M, Zheng B, Moriyama T, Fujita H, Manabe T, Ohtsuka T, Shimamoto M, Miyazaki T, Mizumoto K, Oda Y, Nakamura M.
  • Journal Title: Int J Oncol Volume: 48 Issue: 4 Pages: 1499-1508
  • DOI: 10.3892/ijo.2016.3374
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 膵癌の浸潤・転移における癌微小環境の新たな役割 (2015)
  • Author(s): 大内田研宙、大塚隆生、橋爪誠、中村雅史
  • Journal Title: 胆と膵 Volume: 36 Pages: 1181-1187
• [Presentation] Autophagy Drives Pancreatic Stellate Cells Activation and Promotes Pancreatic Cancer (2016)
  • Author(s): Endo S,Nakata K,Ohuchida K,Ando Y,Kibe S,Takesue S,Nakayama H,Abe T,Koikawa K,Okumura T,Mizuuchi Y,Moriyama T,Miyasaka Y,Manabe T,Ohtsuka T,Nagai E,Mizumoto K,Oda Y,Nakamura M
  • Organizer: 47th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Boston(USA)
  • Year and Date: 2016-10-28
  • Int'l Joint Research
• [Presentation] 膵星細胞におけるオートファジーは，膵癌の成長と転移を促進する (2016)
  • Author(s): 遠藤翔
  • Organizer: 第７１回日本消化器外科学会総会
  • Place of Presentation: アステイ徳島(徳島市)
  • Year and Date: 2016-07-15
• [Presentation] サリノマイシンは膵癌細胞のオートファジーを亢進させ、癌細胞増殖を抑制する (2016)
  • Author(s): 遠藤翔 他
  • Organizer: 第107回日本消化器病学会九州支部例会
  • Place of Presentation: ホテルグランデはがくれ(佐賀市)
  • Year and Date: 2016-06-24
• [Presentation] 膵癌の癌関連線維芽細胞におけるオートファジーの役割 (2016)
  • Author(s): 遠藤翔、仲田興平、大内田研宙、佐田政史、水内祐介、大塚隆生、植木隆、永井英司、水元一博、小田義直、中村雅史
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: リーガロイヤルホテル大阪(大阪市）
  • Year and Date: 2016-04-16
• [Presentation] Pancreatic Stellate Cells Lead and Promote the Local Invasion of Cancer Cells, by Physically Remodeling the Extracellular Matrix with Collagen Fiber Alignment in Pancreatic Cancer (2015)
  • Author(s): Koikawa K, Ohuchida K, Sada M, Abe T, Endo S, Horioka K, Moriyama T, Miyasaka Y, Ohtsuka T, Ohuchida R, Ueki T, Nagai E, Mizumoto K, Nakamura M
  • Organizer: American Pancreatic Association 46th Annual Meeting
  • Place of Presentation: San Diego(USA)
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Suppression of CD51 in Pancreatic Stellate Cells Inhibits Tumor Growth by Reducing Stroma and Altering Tumor-Stromal Interaction in Pancreatic Cancer (2015)
  • Author(s): Horioka K, Ohuchida K, Sada M, Zheng B, Ohtsuka T, Ueki T, Nagai E, Mizumoto K, Oda Y, Nakamura M
  • Organizer: American Pancreatic Association 46th Annual Meeting
  • Place of Presentation: San Diego(USA)
  • Year and Date: 2015-11-04
  • Int'l Joint Research