The development of pancreatic cancer therapy based on regulating extracellular matrix remodeling by pancreatic stellate cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462117
• 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: MIYASAKA Yoshihiro 九州大学, 医学(系)研究科(研究院), 助教 (40507795)
• Co-Investigator(Kenkyū-buntansha): TANAKA Masao 九州大学, 医学研究院, 教授 (30163570) ; NAKATA Kohei 九州大学, 大学病院, 特別教員 (30419569)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 膵癌 / 膵星細胞 / 細胞外マトリックス / 低酸素 / PLOD2

Outline of Final Research Achievements

We generate cell-free 3D matrices from PSCs. The cell-free 3D matrices containing abundant fibronectin and collagen fibers closely resembled in vivo stromal matrices. To assess the impact of hypoxia on ECM organization, we measured fibronectin fiber orientation in 3D matrices derived from PSCs. We found that 3D matrices from PSCs under hypoxia displayed an organized parallel fibronectin orientation compared with random fiber arrangement in the 3D matrices derived from PSCs under normoxia. Cancer cells movement within 3D matrices derived from PSCs under hypoxia was directionally persistent. PLOD2 in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3D matrices, leading to decreased directional migration of cancer cells within the matrices.

Free Research Field

医歯薬学