A new strategy for improving the efficacy of the conventional therapy of pancreatic cancer by remodeling its microenvironment

• Project/Area Number: 25670586
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: TANAKA Masao 九州大学, 医学(系)研究科(研究院), 教授 (30163570)
• Co-Investigator(Kenkyū-buntansha): TAKAHATA Shunichi 九州大学, 大学病院, 講師 (50437779) ; UEDA Junji 佐賀大学, 医学部, 准教授 (90529801) ; MANABE Tatsuya 九州大学, 医学研究院, 助教 (60546464) ; SHIRAHANE Kengo 九州大学, 医学研究院, 共同研究員 (10529803) ; OHUCHIDA Kenoki 九州大学, 大学病院, 助教 (20452708)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 膵癌 / 膵星細胞 / 癌微小環境 / リモデリング / 治療抵抗性 / 遺伝子改変マウス / CD51

Outline of Final Research Achievements

In genetically engineered mouse model of pancreatic cancer, the histopathological findings, including pancreatic intraepithelial neoplasia and a lot of fibrous tissue in the tumor stroma, were similar to those of human.
Integrin alpha v was widely expressed in the stroma of pancreatic cancer. Knockdown of integrin alpha v in pancreatic stellate cells decreased the production of extracellular matrix such as collagenⅠand fibronectin. PDGFA, a growth factor related to cancer-stromal interaction, and CTGF, a profibrotic growth factor, were also down-regulated by knockdown of integrin alpha v. When pancreatic cancer cells and pancreatic stellate cells were co-transplanted subcutaneously into nude mice, knockdown of integrin alpha v in pancreatic stellate cells decreased the tumor growth as compared with the control.

Research Products

• [Journal Article] Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer. (2014)
  • Author(s): Akagawa S, Ohuchida K, Torata N, Hattori M, Eguchi D, Fujiwara K, Kozono S, Cui L, Ikenaga N, Ohtsuka T, Oishima S, Mizumoto K, Oda Y, Tanaka M
  • Journal Title: Int J Oncol Volume: 45 Issue: 1 Pages: 113-120
  • DOI: 10.3892/ijo.2014.2391
  • Peer Reviewed / Acknowledgement Compliant
• [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
• [Journal Article] CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells. (2014)
  • Author(s): Fujiwara K, Ohuchida K, Sada M, Horioka K, Ulrich CD 3rd, Shindo K, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, Tanaka M.
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: 1-11
  • DOI: 10.1371/journal.pone.0107247
  • Peer Reviewed / Open Access
• [Journal Article] Pirfenidone inhibits desmoplasia of pancreatic cancer by regulating stellate cells. (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Ming Zhao, Lin Cui, Koji Shindo, Kazuhiro Mizumoto, and Masao Tanaka
  • Journal Title: Cancer Research Volume: 73 Issue: 7 Pages: 2345-2356
  • DOI: 10.1158/0008-5472.can-12-3180
  • Peer Reviewed
• [Presentation] 膵癌関連繊維芽細胞におけるCD146発現と膵がんの進展抑制 (2014)
  • Author(s): 鄭彪、大内田研宙、崔林、水内祐介、藤原謙次、赤川進、堀岡宏平、田中友晴、佐田政史、仲田興平、前山良、大塚隆生、小田義直、水元一博、田中雅夫
  • Organizer: 第45回日本膵臓学会大会
  • Place of Presentation: 北九州市
  • Year and Date: 2014-07-11
• [Presentation] トラニラストによる膵星細胞の抑制についての検討 (2014)
  • Author(s): 田中友晴、大内田研宙、水元一博、奥村隆志、千々岩芳朗、吉田真樹、佐田政史、堀岡宏平、鄭彪、赤川進、藤原謙次、仲田興平、宮坂義浩、前山良、大塚隆生、田中雅夫
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2014-04-04
• [Presentation] 膵癌間質の線維配列が癌細胞の形態と浸潤方向に与える影響 (2014)
  • Author(s): 佐田政史、大内田研宙、堀岡宏平、田中友晴、鄭彪、Cases AI、赤川進、藤原謙次、仲田興平、宮坂義浩、前山良、大塚隆生、高畑俊一、水元一博、田中雅夫
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2014-04-04
• [Presentation] The development of pancreatic cancer therapy based on regulating pancreatic cancer desmoplasia by targeting pancreatic Stellate Cells
  • Author(s): Shingo Kozono
  • Organizer: International Pancreatic Research Forum 2013
  • Place of Presentation: Sendai
  • Invited
• [Presentation] Regulation of Pancreatic Stellate cells for Treatment of Pancreatic cancer
  • Author(s): Kenoki Ohuchida
  • Organizer: The 6th International Conference and Commemorative Lecture of Pin-Wen Lin of Pancreatic Cancer
  • Place of Presentation: Taiwan
  • Invited