The mechanism of promoting remote metastasis by exosome derived from pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08684
• 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, 講師 (50433389)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵臓がん / エクソソーム / 遠隔転移

Outline of Final Research Achievements

The overall concept of the research is to clarify the mechanism of distant metastasis of pancreatic cancer cells and to create novel therapeutic strategies. Pancreatic cancer has the poorest prognosis among solid tumors, with a 5-year survival rate of less than 10%, and distant metastasis and local invasion determine the prognosis. In this study, we aim to elucidate the molecular mechanism of early distant metastasis by focusing on exosomes secreted by pancreatic cancer cells. We have already established 10 different pancreatic cancer stem cell lines from pancreatic cancer patients resistant to the anticancer drug gemcitabine (GEM). We have also generated mouse engineered pancreatic cancer stem cell lines by transferring oncogenes into CD133-positive mouse pancreatic tissue stem cells. We will elucidate the molecular mechanisms of the early stages of metastasis using exosomes derived from the human and mouse pancreatic cancer stem cell lines we established.

Free Research Field

がんの細胞生物学

Academic Significance and Societal Importance of the Research Achievements

膵臓がんは臓器別死亡数の第４位にあり、早期診断が困難で予後不良の疾患であり、発見時には多くの症例ですでに遠隔転移や癌性腹膜炎を伴っている。予後を左右する遠隔転移の病態解明や新しい治療法の開発が急務である。最近、がん細胞が細胞間コミュニケーションをはかるツールとして細胞が分泌するエクソソームが注目されている。本研究では、我々が樹立したヒトやマウスの膵臓がん細胞由来のエクソソームが初期の転移にどのように関与するのかを明らかにした。