Relationship between stromal cells and pancreatic cancer cells in metastasis and dissemination

• Project/Area Number: 15K10185
• 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: MORIYAMA Taiki 九州大学, 大学病院, 准教授 (70586859)
• Co-Investigator(Kenkyū-buntansha): 藤田 逸人 九州大学, 医学研究院, 助教 (40611281) ; 坂井 寛 九州大学, 医学研究院, 共同研究員 (80611665) ; 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: 膵癌 / 間質細胞 / 膵星細胞 / 腹膜中皮細胞 / 湿潤・転移 / 腹膜播種 / リモデリング / 転移 / Endo180 / 膵臓癌 / 繊維芽細胞 / 播種

Outline of Final Research Achievements

Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180. Cancer-associated peritoneal mesothelial cells lead the formation of pancreatic cancer peritoneal dissemination by cancer interstitial interaction and microenvironment alteration. Furthermore, we identified autophagy was involved in the activation of pancreatic stellate cells. In the mouse model, suppression of autophagy of pancreatic stellate cells reduced tumor development and metastasis. From these results, we clarified the possibility of a new treatment targeting stroma.

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] 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] 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] Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL. (2016)
  • Author(s): Chijiiwa Y, Moriyama T, Ohuchida K, Nabae T, Ohtsuka T, Miyasaka Y, Fujita H, Maeyama R, Manabe T, Abe A, Mizuuchi Y, Oda Y, Mizumoto K, Nakamura M
  • Journal Title: Int J Oncol Volume: 48 Issue: 4 Pages: 1688-1700
  • DOI: 10.3892/ijo.2016.3389
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] 膵オルガノイドによる新たな膵癌局所微小浸潤機序の解明‐膵星細胞が誘導する基底膜破壊と間質浸潤‐ (2017)
  • Author(s): 肥川和寛、大内田研宙、岐部晋、安藤陽平、武居晋、中山宏道、阿部俊也、遠藤翔、奥村隆志、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117回日本外科学会定期学術集会
• [Presentation] 膵癌局所浸潤を先導するleading cell －膵星細胞がつくる膵癌局所微少環境の機序解明－ (2017)
  • Author(s): 肥川和寛、大内田研宙、安藤陽平、岐部晋、中山宏道、武居晋、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38回癌免疫外科研究会
• [Presentation] 膵星細胞におけるEndo180発現の意義および治療標的因子としての検討 (2017)
  • Author(s): 肥川和寛、大内田研宙、安藤陽平、岐部晋、中山宏道、武居晋、阿部俊也、遠藤翔、奥村隆志、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] 膵星細胞が誘導する新たな膵癌局所微小浸潤機序の解明 (2017)
  • 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25回日本消化器関連学会週間 第15回日本消化器外科学会大会
• [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] Novel role of peritoneal mesothelial cells that lead to pancreatic cancer peritoneal dissemination formation. (2016)
  • Author(s): Abe T, Ohuchida K, Kibe S, Ando Y, Nakayama H, Takesue S, Endo S, Koikawa K, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, 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] Endo180 regulate phosphorylation of myosin light chain 2 activity and increase the ability of extracellular matrix remodeling in leading pancreatic stellate cells. (2016)
  • Author(s): Koikawa K, Ohuchida K, Kibe S, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Nakamura M
  • Organizer: 47th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Boston(USA)
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] 膵癌腹膜播種形成を導く腹膜中皮細胞の新たな役割～防御から促進へ～ (2016)
  • Author(s): 阿部俊也、大内田研宙、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、奥村隆志、堀岡宏平、佐田政史、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] Comparison of Surgical Outcome of Radical Antegrade Modular Pancreatosplenectomy with Standard Retrograde Pancreatosplenectomy and Evaluation of the Prognostic Factors in Left Side Pancreatic Cancer (2015)
  • Author(s): Abe T, Ohuchida 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] 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