Elucidation of G0 phase maintenance mechanism by autophagy in cancer stem cells and development of artificial virus therapy method

• Project/Area Number: 25713050
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: NAKATA Kohei 九州大学, 大学病院, 助教 (30419569)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2013: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: オートファジー / 癌幹細胞 / 膵臓癌 / 膵癌 / 細胞周期 / Drug Delivary System / 人工ウイルス / 癌

Outline of Final Research Achievements

Traditional chemotherapy is ineffective to cancer stem cells, because these cells maintain the cell cycle in G0 phase. Therefore, we aimed to elucidate the G0 phase maintenance mechanism of cancer stem cells and to develop a method to improve the treatment resistance of cancer stem cells, in order to prevent recurrence of cancer.
We reported that the autophagy inhibitor suppressed tumor growth in mice orthotopically transplanted pancreatic cancer models. Furthermore, we reported that cancer cells in the proliferation phase decreased in these tumor section, suggesting the possibility that cells in the G0 phase are increasing.

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] 膵癌におけるmiRNA発現と上皮間葉転換 (2015)
  • Author(s): 仲田興平、大内田研宙、大塚隆生、中村雅史
  • Journal Title: 胆と膵 Volume: 36 Pages: 1117-1122
• [Journal Article] Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion (2014)
  • Author(s): Nakata K, Ohuchida K, Mizumoto K, Aishima S, Oda Y, Nagai E, Tanaka M
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: S4 Pages: 564-574
  • DOI: 10.1245/s10434-014-3676-8
  • Peer Reviewed
• [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
• [Presentation] 膵周囲脂肪組織は肝癌細胞の遊走・浸潤機能を増強し、局所浸潤に関与する (2016)
  • Author(s): 奥村隆志、大内田研宙、武居晋、中山宏道、阿部俊也、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、鄭彪、佐田政史、堀岡宏平、森山大樹、三好圭、宮坂義浩、真鍋達也、大塚隆生、植木隆、永井英司、水元一博、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] 膵星細胞は基質リモデリングにより、leading cell として膵癌浸潤を先導する (2016)
  • Author(s): 肥川和寛、大内田研宙、佐田政史、阿部俊也、遠藤翔、奥村隆志、堀岡宏平、森山大樹、宮坂義浩、真鍋達也、大塚隆生、大内田理一、植木隆、永井英司、水元一博、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: 2016-04-14
• [Presentation] calpain阻害剤であるcalpainによる膵癌細胞及び膵星細胞への抑制効果の検討 (2016)
  • Author(s): 吉田真樹、大内田研宙、千々岩芳朗、奥村隆志、田中友晴、佐田政史、堀岡宏平、藤原謙次、森山大樹、宮坂義浩、大塚隆生、高畑俊一、小田義直、水元一博、田中雅夫
  • 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: 2016-04-14
• [Presentation] オートファジーが膵癌の癌間質相互作用に与える影響の検討 (2015)
  • Author(s): 遠藤翔、仲田興平、大内田研宙、阿部俊也、肥川和寛、堀岡宏平、水内祐介、小田義直、水元一博、田中雅夫
  • Organizer: 第46回日本膵臓学会大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-06-19