Development of novel therapeutic agent targeting pancreatic cancer stroma by screening compound library

• Project/Area Number: 15K10188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: TOMINAGA Yohei 九州大学, 医学研究院, 共同研究員 (90304823)
• Co-Investigator(Kenkyū-buntansha): 森山 大樹 九州大学, 大学病院, 准教授 (70586859) ; 水元 一博 九州大学, 大学病院, 准教授 (90253418) ; 大内田 研宙 九州大学, 大学病院, 講師 (20452708)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 化合物ライブラリー / 癌間質相互作用 / 間質標的治療 / 膵星細胞 / 化合物スクリーニング / オートファジー / 脂肪滴

Outline of Final Research Achievements

In the present study, we demonstrated that cancer-associated stroma would become a new target for the treatment of pancreatic cancer. We focused on pancreatic stellate cells(PSCs) as a therapeutic target and developed a novel screening assay system to detect the activation of PSCs. Then we performed high-throughput screening using this assay, and we showed 152 compounds led PSCs into quiescent state. These data suggest that the drugs targeting PSCs may become a novel strategy for pancreatic cancer therapy.

Research Products

• [Journal Article] Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells (2017)
  • Author(s): Endo Sho、Nakata Kohei、Sagara Akiko、Koikawa Kazuhiro、Ando Yohei、Kibe Shin、Takesue Shin、Nakayama Hiromichi、Abe Toshiya、Okumura Takashi、Moriyama Taiki、Miyasaka Yoshihiro、Ohuchida Kenoki、Ohtsuka Takao、Mizumoto Kazuhiro、Nakamura Masafumi
  • Journal Title: Pancreatology Volume: 17 Issue: 6 Pages: 990-996
  • DOI: 10.1016/j.pan.2017.08.009
  • Peer Reviewed
• [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] 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
• [Presentation] 脂肪組織由来幹細胞は膵癌における癌関連線維芽細胞の供給源となり腫瘍形成を促進する (2017)
  • Author(s): 肥川和寛、奥村隆志、大内田研宙、岐部晋、森山大樹、仲田興平、宮坂義浩、真鍋達也、大塚隆生、永井英司、水元一博、中村雅史
  • Organizer: 第48回日本膵臓学会大会
• [Presentation] オートファジーは膵星細胞の活性化に関与しており、その抑制は膵癌の進展を制御する (2017)
  • Author(s): 仲田興平、遠藤翔、大内田研宙、水元一博、小田義直、橋爪誠、中村雅史
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Pancreatic organoids elucidate the new mechanisms of pancreatic cancer local invasion (2017)
  • Author(s): Koikawa K, Ohuchida K, Ando Y, Kibe S, Nakayama H, Takesue S, Yan Z, Abe T, Okumura T, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Okabe Y, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: The 48th Annual Meeting of The American Pancreatic Association
  • Int'l Joint Research
• [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: 2016-10-26
  • Int'l Joint Research
• [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、佐田政史、大内田研宙、阿部俊也、肥川和寛、奥村隆志、佐田政史、堀岡宏平、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