Classification of pancreatic ductal adenocarcinoma based on niche factor dependency with single cell analysis and organoid

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: MIYOSHI Kei 九州大学, 医学研究院, 共同研究員 (70755272)
• Co-Investigator(Kenkyū-buntansha): 進藤 幸治 九州大学, 大学病院, 助教 (00788432) ; 水元 一博 国際医療福祉大学, 赤坂心理・医療福祉マネジメント学部, 教授 (90253418)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵癌 / オルガノイド / 癌関連線維芽細胞 / 癌微小環境 / 微小環境因子 / 膵癌Subtype

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma is characterized by stromal hyperplasia, which is known to increase malignancy via cancer-stromal interactions. The relationship between differentiation type of pancreatic cancer and stroma is still unclear. In this study, we aimed to clarify the influence of the stroma on pancreatic cancer. We established organoids from human pancreatic cancer tumors and classified them into poorly differentiated, intermediate differentiated, and well differentiated types according to the differentiation level, and found that the differentiation level tends to depend on niche factors produced by cancer-associated fibroblasts. In addition, well differentiated tumors, which were more dependent on niche factors, showed increased expression of genes related to mevalonate pathway and were more sensitive to mevalonate metabolism inhibitors, suggesting that they may be useful as targets for subtype-specific therapy for pancreatic cancer.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では膵癌のうち微小環境因子への依存度が高い高分化型の症例において、メバロン酸代謝遺伝子の発現が亢進メバロン酸代謝阻害薬に対する感受性が高いことを示している。このことは微小環境因子によって誘導される分子生物学的特徴が、サブタイプ別治療の治療標的として有用である可能性を示唆しており新たな膵癌治療薬の開発へ結びつく可能性がある。