Identifying the leading cell for the invasion of pancreatic cancer

• Project/Area Number: 24390318
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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): NAGAI Eishi 九州大学, 医学研究院, 准教授 (30264021) ; OHTSUKA Takao 九州大学, 大学病院, 助教 (20372766) ; EGAMI Takuya 九州大学, 医学研究院, 共同研究員 (40507787) ; MORIYAMA Taiki 九州大学, 大学病院, 助教 (70586859) ; TOMINAGA Yohei 九州大学, 医学研究院, 共同研究員 (90304823) ; OHUCHIDA Kenoki 九州大学, 大学病院, 助教 (20452708) ; SHIRAHANE Kengo 九州大学, 医学研究院, 共同研究員 (10529803)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 膵癌 / 浸潤 / 上皮間葉移行 / 膵星細胞 / 細胞外基質 / リーディングセル / コラーゲン / 上皮間葉転換

Outline of Final Research Achievements

We investigated the ability of collagen internalization in pancreatic stellate cells which play a central role in pancreatic cancer desmoplasia to identify the cell which leads the cancer cell invasion. Pancreatic stellate cells had a strong ability for collagen internalization compared to the cancer cells. 98.5% of stellate cells internalized collagen beads while the proportion of cancer cells were 14.4% and 36.2%. The ability of collagen internalization was increased by inducing epithelial-mesenchymal transition, and decreased when the expression of Endo180, a collagen uptake receptor, was suppressed by RNA interference. Leading cell was the pancreatic stellate cell and cancer cells invaded behind the stellate cell when they were cocultured in the three-dimensional collagen gel culture system. In conclusion, our data suggested that pancreatic stellate cell led the invasion of pancreatic cancer cells.

Research Products

• [Journal Article] Anterior gradient 2 downregulation in a subset of pancreatic ductal adenocarcinoma is a prognostic factor indicative of epithelial-mesenchymal transition. (2015)
  • Author(s): Mizuuchi Y, Aishima S, Ohuchida K, Shindo K, Fujino M, Hattori M, Miyazaki T, Mizumoto K, Tanaka M, Oda Y
  • Journal Title: Laboratory Investigation Volume: 95(2) Issue: 2 Pages: 193-206
  • DOI: 10.1038/labinvest.2014.138
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pancreatic Cancer: Clinical Significance of Biomarkers (2014)
  • Author(s): Mori M, Chiba T, Nakamizo A, Kumashiro R, Murata M, Akahoshi T, Tomikawa M, Ohuchida K, Ohtsuka T,Mizumoto K, Hashizume M,Tanaka M
  • Journal Title: Gastro Intestinal Tumors Volume: 1 Issue: 1 Pages: 33-40
  • DOI: 10.1159/000354996
  • Peer Reviewed
• [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] Pancreatic cancer cells enhance the ability of collagen internalization via epithelial-mesenchymal transition. (2012)
  • Author(s): Ikenaga N
  • Journal Title: Plos One Volume: 7 Issue: 7 Pages: 491-499
  • DOI: 10.1371/journal.pone.0040434
  • 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] 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] Pancreatic Cancer Cells Enhance the Ability of Collagen internalization during Epithelial -Mesenchymal Transition (2012)
  • Author(s): Naoki Ikenaga
  • Organizer: 2012 Joint Meeting of American Pancreatic Association and International Association of Pancreatology
  • Place of Presentation: Miami, USA
  • Year and Date: 2012-11-01
• [Presentation] ＣＤ166陰性膵癌細胞は強い浸潤能・遊走能を有する
  • Author(s): 藤原謙次
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡市
• [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: 福岡市
• [Presentation] The investigation of CD146 in pancreatic cancer associated fibroblast
  • Author(s): 趙茗
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡市
• [Book] Annual Review 消化器2014 (2014)
  • Author(s): 佐田政史、水元一博、大内田研宙、大塚隆生、田中雅夫
  • Total Pages: 306
  • Publisher: 中外医学社