Elucidation of leading cell and cancer microenvironment normalization of pancreatic cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293305
• 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: OHUCHIDA Kenoki 九州大学, 大学病院, 助教 (20452708)
• Co-Investigator(Kenkyū-buntansha): 大塚 隆生 九州大学, 大学病院, 講師 (20372766) ; 村田 正治 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (30304744) ; 前山 良 九州大学, 医学(系)研究科(研究院), 共同研究員 (10611668) ; 田中 雅夫 九州大学, 医学(系)研究科(研究院), 教授 (30163570) ; 江上 拓哉 九州大学, 医学(系)研究科(研究院), 共同研究員 (40507787) ; 宮坂 義浩 九州大学, 医学(系)研究科(研究院), 助教 (40507795) ; 真鍋 達也 九州大学, 医学(系)研究科(研究院), 助教 (60546464) ; 坂井 寛 九州大学, 医学(系)研究科(研究院), 共同研究員 (80611665)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Pancreatic cancer / PSCs / Leading cell / ECM remodeling / Cancer micro environment / Normalization

Outline of Final Research Achievements

We established 3D in vitro collagen invasion assay to investigate leading cell. We found that Pancreatic stellate cells (PSCs) frequently invaded a collagen matrix with cancer cells, which invaded behind the invading PSCs, and an increase in the number of invading cancer cells in co-cultures with PSCs. Invading PSCs changed the alignment of collagen fibers, resulting in ECM remodeling and an increase in the parallel fibers along the direction of invading PSCs. We elucidate that one of the ECM remodeling factor of PSCs is Endo180. Endo180 knockdown in PSCs attenuated the invasive abilities of PSCs and co-cultured cancer cells, and decreased the expression level of phosphorylated myosin light chain 2 (MLC2). Our findings suggest that PSCs lead the local invasion of pancreatic cancer cells by physically remodeling the ECM, possibly via the function of Endo180, which reconstructs the actin cell skeleton by phosphorylation of MLC2.

Free Research Field

医歯薬学