Elucidation of selection mechanism of disseminated cancer cells in metastatic organs

• Project/Area Number: 26462064
• 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: ONIMARU Manabu 九州大学, 医学研究院, 共同研究員 (80529876)
• Co-Investigator(Kenkyū-buntansha): 江上 拓哉 九州大学, 医学研究院, 共同研究員 (40507787) ; 真鍋 達也 九州大学, 大学病院, 講師 (60546464)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / 肝転移 / CD110 / トロンボポエチン(TPO) / ERK / MYC / 癌幹細胞 / トロンボポエチン

Outline of Final Research Achievements

To elucidate the mechanism of liver metastasis of pancreatic cancer, we focused on thrombopoietin (TPO) and its receptor CD 110 in pancreatic cancer.
In resected specimens of pancreatic cancer, high expression of CD110 was an independent poor prognostic factor and independent predictor of liver metastasis. Inhibition of CD110 expression in pancreatic cancer cells significantly reduced migration / invasion ability of pancreatic cancer cells. In CD110-positive pancreatic cancer cells, ERK and MYC were activated by TPO administration, and cell proliferation was increased. These results suggested that TPO - CD110 - ERK - MYC signal might be involved in liver metastasis in pancreatic cancer.

Research Products

• [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] TM4SF1 as a prognostic marker of pancreatic ductal adenocarcinoma is involved in migration and invasion of cancer cells (2015)
  • Author(s): Zheng B, Ohuchida K, Cui L, Zhao M, Shindo K, Fujiwara K, Manabe T, Torata N, Moriyama T, Miyasaka Y, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, Tanaka M
  • Journal Title: Int J Oncol. Volume: 47 Issue: 2 Pages: 490-498
  • DOI: 10.3892/ijo.2015.3022
  • Peer Reviewed
• [Presentation] 肝癌におけるCD110の臨床的意義と癌進展におけるその役割 (2016)
  • Author(s): Zilong Yan、大内田研宙、Zheng Biao、堀岡宏平、佐田政史、奥村隆志、千々岩芳朗、吉田真樹、遠藤翔、肥川和寛、阿部俊也、中山宏道、武居晋、森山大樹、宮坂義浩、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] 膵癌肝転移に関わるmicroRNAとその標的分子の同定 (2016)
  • Author(s): 千々岩芳朗，大内田研宙、森山大樹、佐田政史、堀岡宏平、鄭彪、奥村隆志、吉田真樹、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] 低酸素誘導性LOXによる癌間質リモデリングが膵癌膵癌浸潤能に与える影響の検討 (2015)
  • Author(s): 佐田政史、大内田研宙、阿部俊也、遠藤翔、肥川和寛、奥村隆志、千々岩芳朗、吉田真樹、堀岡宏平、水内祐介、宮坂義浩、眞鍋達也、大塚隆生、高畑俊一、植木隆、 永井英司、水元一博、小田義直、中村雅史、田中雅夫
  • Organizer: JDDW2015 第23回消化器関連学会週間
  • Place of Presentation: 東京都
  • Year and Date: 2015-10-08
• [Presentation] 膵癌細胞の浸潤機序-浸潤を先導するleading cellsの同定・解析- (2015)
  • Author(s): 肥川和寛、佐田政史、大内田研宙、阿部俊也、遠藤翔、真鍋達也、大塚隆生、高畑俊一、植木隆、永井英司、水元一博、中村雅史、田中雅夫
  • Organizer: JDDW2015 第23回消化器関連学会週間
  • Place of Presentation: 東京都
  • Year and Date: 2015-10-08
• [Presentation] 脂肪組織由来幹細胞は膵癌細胞の遊走・浸潤を促進し悪性度に関与する (2015)
  • Author(s): 奥村隆志、大内田研宙、阿部俊也、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、佐田政史、堀岡宏平、真鍋達也、大塚隆生、高畑俊一、植木隆、永井英司、水元一博、中村雅史、田中雅夫
  • Organizer: JDDW2015 第23回消化器関連学会週間
  • Place of Presentation: 東京都
  • Year and Date: 2015-10-08
• [Presentation] MALDI mass spectrometry imagingによる凍結組織アレイ包埋乳がん組織の低分子代謝産物プロファイリング (2015)
  • Author(s): 寅田信博、久保 真、三浦大典、大内田研宙、宮崎哲之、藤村由紀、早川英介、大塚 隆生、宮坂義浩、真鍋達也、小田義直、水元一博、中村雅史
  • Organizer: 第40回日本医用マススペクトル学会年会
  • Place of Presentation: 浜松市
  • Year and Date: 2015-09-17