Development of order-made therapy for pancreatic cancer controlling of crosstalk between cancer cell and cancer associated fibroblast

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10588
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: Motoi Fuyuhiko 東北大学, 医学系研究科, 准教授 (30343057)
• Co-Investigator(Kenkyū-buntansha): 立川 正憲 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (00401810) ; 大塚 英郎 東北大学, 大学病院, 助教 (50451563)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 膵癌

Outline of Final Research Achievements

Platelet-derived growth factor receptor beta (PDGFRβ) and hepatocyte growth factor receptor (MET) expressed on cancer-associated fibroblast (CAFs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and CAFs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRβ, on the interaction between PCCs and CAFs. In CAFs, PDGFRβ and MET were upregulated compared with other receptor tyrosine kinases. Conditioned medium from CAFs promoted the proliferation of PCCs, and vice versa. Moreover, MK2461 suppressed the effects of conditioned medium on PCCs and CAFs. Finally, MK2461 significantly inhibited tumor growth in mice coinjected with PCCs and CAFs.
The PDGFRβ and MET may play a critical role in the interaction between PCCs and CAFs, which was modulated by MK2461. Therefore, MK2461 may have therapeutic potential in the treatment of pancreatic cancer.

Free Research Field

膵臓外科

Academic Significance and Societal Importance of the Research Achievements

膵癌は有効な治療法が少なく、難治性癌の代表である。既存薬以外の治療標的を見出すことで、有効薬の創薬につながる可能性がある膵癌と癌関連線維芽細胞に着目した治療戦略は、膵癌治療に重要な役割を果たす可能性が示唆され、これらの経路を制御することで、特異的な治療戦略の開発が期待出来る。代表的難治癌の治療成績向上につながれば、学術的・社会的意義がある。