Establishment of a novel therapeutic strategy for pancreatic cancer phenotyping and regulating the pancreatic stellate cells in the tumor microenvironment

• Project/Area Number: 24592031
• 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 (2014); Kyushu University (2012-2013)
• Principal Investigator: UEDA Junji 佐賀大学, 医学部, 准教授 (90529801)
• Co-Investigator(Kenkyū-buntansha): TANAKA Masao 九州大学, 医学研究院, 教授 (30163570) ; NAGAI Eishi 九州大学, 医学研究院, 准教授 (30264021) ; EGAMI Takuya 九州大学, 医学研究院, 共同研究員 (40507787) ; MIYASAKA Yoshihiro 九州大学, 医学研究院, 助教 (40507795) ; TOMINAGA Yohei 九州大学, 医学研究院, 共同研究員 (90304823)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); 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); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膵癌 / 癌間質相互作用 / 膵星細胞 / CD271 / CD146 / podoplanin / 線維増生

Outline of Final Research Achievements

The aim of this study is classifying the pancreatic stellate cells that are the important factor in the tumor environment, and identifying the specific cell population which strongly enhances the tumor malignancy. CD271 positive pancreatic stellate cells were at the tumor periphery and correlated with patients’ prognosis negatively. CD146 positive pancreatic stellate cells existed around the PanIN lesions and correlated with patients’ prognosis negatively. These findings indicates that pancreatic stellate cells are the functionally heterogenetic population and targeting the specific group of stellate cells could be the novel therapeutic strategy.

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
• [Journal Article] Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas. (2013)
  • Author(s): Shindo K, Aishima S, Ohuchida K, Fujiwara K, Fujino M, Mizuuchi Y, Hatton M, Mizumoto K. Tanaka M, Oda Y.
  • Journal Title: Mol Cancer Volume: 12(1) Issue: 1 Pages: 168-168
  • DOI: 10.1186/1476-4598-12-168
  • Peer Reviewed
• [Journal Article] CD271^+ subpopulation of pancreatic stellate cells correlates with prognosis of pancreatic cancer and is regulated by interaction with cancer cells (2012)
  • Author(s): Kenji Fujiwara
  • Journal Title: PLoS One Volume: 12 Issue: 12 Pages: e52682-e52682
  • DOI: 10.1371/journal.pone.0052682
  • 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] 腹膜繊維芽細胞の作用に着目した膵癌腹膜藩種メカニズムの解明
  • Author(s): 赤川 進
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] 膵癌間質におけるCD90とα-SMA発現の意義
  • Author(s): 佐田 政史
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] 膵癌におけるCD271陽性膵星細胞の意義
  • Author(s): 藤原 謙次 他
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉
• [Presentation] CD271+ pancreatic stellate cells are correlated with prognosis of patients with pancreatic cancer and regulated by interaction with cancer cells
  • Author(s): Kenji Fujiwara et al.
  • Organizer: International Symposium on Pancreas Cancer 2012 in Kyoto
  • Place of Presentation: 京都
• [Presentation] Fibroblasts expressing Podoplanin enhance the tumor progression of invasive ductal carcinoma of pancreas
  • Author(s): 進藤 幸治 他
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌