The role of autophagy in perineural infiltration of pancreatic cancer

• Project/Area Number: 16K10597
• 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: EGAMI Takuya 九州大学, 医学研究院, 共同研究員 (40507787)
• Co-Investigator(Kenkyū-buntansha): 宮坂 義浩 九州大学, 大学病院, 助教 (40507795) ; 大内田 研宙 九州大学, 大学病院, 講師 (20452708)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / 神経浸潤 / オートファジー / 神経細胞

Outline of Final Research Achievements

Pancreatic cancer shows aggressive progression with a very poor prognosis. Perineural infiltration is one of the biggest reason contribute to its miserable outcome, so it is urgently needed to clarify the mechanism of pancreatic cancer invasion. In this study, we focused on the activity of autophagy in pancreatic cancer. We examined its activity and role, both of pancreatic cancer cells and pancreatic stellate cells. We showed that autophagy plays a protective role for pancreatic cancer cells, and also autophagy is involved in pancreatic stellate cell activation. These results play an important role for the elucidation of the process that pancreatic cancer infiltrate into nerves.

Academic Significance and Societal Importance of the Research Achievements

膵癌の5年生存率はここ30年間でほとんど改善が無く、治療法の開発は社会的緊急性・重要度が高い。また、再発形式として神経浸潤を主体とした後腹膜再発が高率にみられることも膵癌の大きな特徴である。この原因のひとつである神経浸潤の制御の機序解明につながる膵癌間質制御のメカニズム解明は膵癌治療成績の向上の一翼を担うと考えられ、それによって得られる社会的意義は非常に高いと考えられる。

Research Products

• [Journal Article] Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion. (2019)
  • Author(s): Kibe S, Ohuchida K, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Okumura T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Shimamoto M, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M.
  • Journal Title: Cancer Lett Volume: 444 Pages: 70-81
  • DOI: 10.1016/j.canlet.2018.12.005
  • Peer Reviewed / Open Access
• [Journal Article] Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix (2018)
  • Author(s): Okumura T, Ohuchida K, Kibe S, Iwamoto C, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Sada M, Horioka K, Mochidome N, Arita M, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M
  • Journal Title: Int J Cancer Volume: 144 Issue: 6 Pages: 1401-1413
  • DOI: 10.1002/ijc.31775
  • Peer Reviewed / Open Access
• [Journal Article] Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180 (2018)
  • Author(s): Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
  • Journal Title: Cancer Letters Volume: 412 Pages: 143-154
  • DOI: 10.1016/j.canlet.2017.10.010
  • Peer Reviewed / Open Access
• [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] Degree of desmoplasia in metastatic lymph node lesions is associated with lesion size and poor prognosis in pancreatic cancer patients (2017)
  • Author(s): Nakayama H, Ohuchida K, Yoshida M, Miyazaki T, Takesue S, Abe T, Endo S, Koikawa K, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Shirahane K, Manabe T, Ohtsuka T, Toma H, Tominaga Y, Nagai E, Mizumoto K, Oda Y, Nakamura M.
  • Journal Title: Oncology Letters Volume: 14 Issue: 3 Pages: 3141-3147
  • DOI: 10.3892/ol.2017.6549
  • 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
• [Presentation] ADM are Classified Three Distinct Phenotypical Profiles Depending on its Different Microenvironment (2018)
  • Author(s): S. Kibe, K. Ohuchida, Y. Ando, S. Takesue, M. Nakayama, T. Abe, S. Endo, K. Koikawa, T. Okumura, C. Iwamoto, K. Shindo, T. Moriyama, K. Nakata, S. Nagai, Y. Miyasaka, M. Shimamoto, T. Ohtsuka, K. Mizumoto, M. Nakamura.
  • Organizer: American Pancreatic Association Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] Fat tissue and pancreatic parenchyma play different roles in pancreatic cancer invasion (2018)
  • Author(s): Ohuchida K, Kibe S, Okumura T, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Nakamura M
  • Organizer: Pancreas 2018
  • Int'l Joint Research
• [Presentation] 膵オルガノイドを用いた浸潤性膵管癌の新たな局所微小浸潤機序の解明 (2018)
  • Author(s): 米永晃子、肥川和寛、大内田研宙、進藤幸治、仲田興平、森山大樹、宮坂義浩、大塚隆生、水元一博、中村雅史
  • Organizer: 第49回日本膵臓学会大会
• [Presentation] マウスモデルを用いた膵癌微小転移形成機序の解析 (2017)
  • Author(s): 武居晋、大内田研宙、安藤陽平、岐部晋、中山宏道、阿部俊也、肥川和寛、遠藤翔、厳子龍、奥村隆志、仲田興平、森山大樹、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117回日本外科学会定期学術集会
• [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