A new strategy in the treatment of pancreatic cancer focused on the tumor vessel remodeling by pericytes

• Project/Area Number: 25462118
• 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: MANABE Tatsuya 九州大学, 医学(系)研究科(研究院), 助教 (60546464)
• Co-Investigator(Kenkyū-buntansha): MIZUMOTO Kazuhiro 九州大学, 大学病院, 准教授 (90253418) ; UEDA Junji 佐賀大学, 医学部, 准教授 (90529801) ; TOMA Hiroki 九州大学, 医学研究院, 共同研究員 (80437780) ; OHUCHIDA Kenoki 九州大学, 大学病院, 助教 (20452708)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / 周皮細胞 / 膵星細胞 / 血管リモデリング / 癌間質相互作用 / 腫瘍血管 / 細胞外基質 / CD51

Outline of Final Research Achievements

In this study, we focused on how the pericytes, which cover the vessels and contribute to their stability, influence the tumor vessels. Pericytes express partially the same marker as cancer-associated fibroblasts(CAFs), which enhance cancer cell malignancy through the tumor-stromal interactions. In our study, NG2/PDGFRβ positive cells were observed in CAFs established from the resected pancreatic cancer specimens, and in the immunohistochemical staining, they were prevalent in the stroma regardless of blood vessels.
Moreover, higher stromal CD51 expression in the resected pancreatic cancer specimens was related to the shorter patients survival time, and the knockdown of CD51 in PSCs resulted in the suppression of proliferation and migration of PSCs in vitro. In addition, we reported that tumor growth in the nude mice co-transplanted with pancreatic cancer cells and CD51 knocked down PSCs was suppressed, compared with those co-transplanted with control PSCs.

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] 膵癌の浸潤・転移における癌微小環境の新たな役割 (2015)
  • Author(s): 大内田研宙、大塚隆生、橋爪誠、中村雅史
  • Journal Title: 胆と膵 Volume: 36 Pages: 1181-1187
• [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