Elucidation and control of the microemviroment of pancreatic cancer

• Project/Area Number: 16K10600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Saga University (2017-2018); Kyushu University (2016)
• Principal Investigator: Manabe Tatsuya 佐賀大学, 医学部, 准教授 (60546464)
• Co-Investigator(Kenkyū-buntansha): 宮坂 義浩 九州大学, 大学病院, 助教 (40507795) ; 森山 大樹 九州大学, 大学病院, 准教授 (70586859) ; 江口 大樹 九州大学, 医学研究院, 共同研究員 (90726390) ; 池永 直樹 九州大学, 医学研究院, 共同研究員 (90759755)
• 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 / 膵癌微小環境 / 治療誘導性secretome / 治療抵抗性 / オルガノイド / 膵星細胞 / 微小浸潤 / 微小環境 / secretome

Outline of Final Research Achievements

Secretome or activity of stromal remodeling may cause reftactory pancreatic cancer. The system of microenvironment around pancreatic cancer was examined regarding therapy-inducible secretome. Using our established microenvironment model, several secretomes affecting cancer invasion and migration were identified. In the future, secretome affecting treatment resistance would be identified as a final goal.

Academic Significance and Societal Importance of the Research Achievements

今回の検討で癌の浸潤、遊走に関わるsecretome因子が複数同定できているので、治療抵抗性に関わるsecretome因子の同定を勧めていき、新たな治療戦略の一助になることを期待する。

Research Products

• [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] Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells. (2017)
  • Author(s): Okumura T, Ohuchida K, Sada M, Abe T, Endo S, Koikawa K, Iwamoto C, Miura D, Mizuuchi Y, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
  • Journal Title: Oncotarget Volume: 8 Issue: 11 Pages: 18280-18295
  • DOI: 10.18632/oncotarget.15430
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Clinical importance of intraoperative peritoneal cytology in patients with pancreatic cancer. (2017)
  • Author(s): Abe T, Ohuchida K, Endo S, Ookubo F, Mori Y, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Oda Y, Nakamura M.
  • Journal Title: Surgery Volume: 161 Issue: 4 Pages: 951-958
  • DOI: 10.1016/j.surg.2016.10.035
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination. (2017)
  • Author(s): Abe T, Ohuchida K, Koikawa K, Endo S, Okumura T, Sada M, Horioka K, Zheng B, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
  • Journal Title: Int J Oncol Volume: 50 Issue: 2 Pages: 457-467
  • DOI: 10.3892/ijo.2016.3829
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] （The） Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer-stromal interactions in a mouse xenograft model (2016)
  • Author(s): Yoshida M, Miyasaka Y, Ohuchida Kenoki, Okumura T, Zheng B, Torata N, Fujita H, Nabae T, Manabe T, Shimamoto M, Ohtsuka T, Mizumoto K, Nakamura M
  • Journal Title: Cancer Sci Volume: 107 Issue: 10 Pages: 1443-1452
  • DOI: 10.1111/cas.13024
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 膵オルガノイドを用いたリアルタイムイメージングによる新たな膵癌局所微小浸潤機序の解明 (2018)
  • Author(s): 肥川和寛, 大内田研宙, 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72回日本消化器外科学会総会
• [Presentation] Pancreatic organoids elucidate the new mechanisms of pancreatic cancer local invasion (2017)
  • Author(s): K Koikawa, K Ohuchida, Y Ando, S Kibe, H Nakayama, S Takesue, Z Yan, T Abe, T Okumura, C Iwamoto, T Moriyama, K Nakata, Y Miyasaka, Y Okabe, T Ohtuka, K Mizumoto, M Nakamura
  • Organizer: The 48th Annual Meeting of The American Pancreatic Association