Normalization of tumor vessels targeting pericytes; a new approach in treatment of pancreatic cancer

• Project/Area Number: 25461024
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: SHIMAMOTO Masaya 九州大学, 大学病院, 助教 (00457433)
• Co-Investigator(Kenkyū-buntansha): MIZUMOTO Kazuhiro 九州大学, 大学病院, 准教授 (90253418) ; SAKAI Hiroshi 九州大学, 医学研究院, 共同研究員 (80611665)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / ペリサイト / 膵星細胞 / 薬剤送達 / 血管内皮細胞 / 腫瘍血管 / 間質 / NG2 / PDGFRβ

Outline of Final Research Achievements

Antiangiogenic agents have been shown to be effective in the treatment of cancers such as colon cancer and lung cancer, but not in pancreatic cancer. In this study, we aimed to develop a new treatment of pancreatic cancer targeting pericytes, which cover and stabilize the tumor vessels.
In our study, pericytes were prevalent in the stroma of pancreatic cancer specimen. Then we conducted this study focused on pancreatic stellate cells(PSCs),which play a crucial role in desmoplasia, considering the possiblity that tumor vascular permeability is caused by the abundant tumor stroma.
Stromal CD51 expression in the resected pancreatic cancer specimens was associated with shorter patients survival time, and knockdown of CD51 in PSCs led to suppression of proliferation and migration of PSCs in vitro. In addition, tumor growth was inhibited in nude mice co-transplanted with pancreatic cancer cells and CD51 knocked down PSCs, compared with those co-transplanted with control PSCs.

Research Products

• [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] 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] 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
• [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
• [Presentation] 膵癌におけるTM4SF1発現の意義 (2014)
  • Author(s): 鄭彪、崔林、大内田研宙、進藤幸治、藤原謙次、赤川進、堀岡宏平、田中友晴、佐田政史、吉田真樹、千々岩芳朗、奥村隆志、仲田興平、大塚隆生、小田義直、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] 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