Pancreatic cancer derived exosomes promote early liver metastasis

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08705
• 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: Kobe University
• Principal Investigator: Hori Yuichi 神戸大学, 保健学研究科, 教授 (80248004)
• Co-Investigator(Kenkyū-buntansha): 清水 一也 神戸大学, 保健学研究科, 保健学研究員 (50335353) ; 三好 真琴 神戸大学, 保健学研究科, 助教 (50433389)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 膵臓がん / エクソソーム / 遠隔転移 / 肝転移

Outline of Final Research Achievements

Pancreatic cancer is the fourth leading cause of cancer mortality in Japan, and distant metastasis is a major prognostic factor. Recently, it has been revealed that all cells secrete tiny extracellular vesicles called exosomes for intercellular communication, and various reports have been published on cancer cells. In this study, we were able to reconstruct pre-metastatic niche in the liver using exosomes derived from (1) a human pancreatic cancer stem cell line that we established and (2) a mouse artificial pancreatic cancer stem cell line generated by oncogene transfer to pancreatic-tissue specific stem cells. The metastatic mechanism such as epithelial-mesenchymal transition was also elucidated at the molecular level. The results of this research will lead to the development of therapeutic drugs targeting exosomes and contribute to the improvement of the prognosis of pancreatic cancer.

Free Research Field

膵臓外科学

Academic Significance and Societal Importance of the Research Achievements

手術、抗がん剤、放射線治療の進歩にもかかわらず、膵臓癌の５年生存率は未だ10%以下で、固形癌の中で最も予後不良と言われる。今後も罹患数や死亡数は増加すると世界中で予測されており、肝臓や肺などへの転移や神経浸潤といった膵臓癌に特徴的な病態の解明やその対策が待たれる。本研究では、膵臓癌の転移機構を明らかにするため、膵臓癌が分泌するエクソソームと呼ばれる微小な小胞に着目して実験を行った。その結果、エクソソーム投与により、転移のプロセスが亢進することが判明した。この成果はエクソソームを標的とした治療薬の開発に繋がり、膵臓癌の予後改善に貢献できる。