Elucidation of pathogenesis and identification of therapeutic targets in colorectal mucinous carcinoma by establishing organoids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06924
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Oita University
• Principal Investigator: Akagi Tomonori 大分大学, 医学部, 講師 (80572007)
• Co-Investigator(Kenkyū-buntansha): 塚本 善之 大分大学, 医学部, 助教 (00433053) ; 猪股 雅史 大分大学, 医学部, 教授 (60315330) ; 泥谷 直樹 大分大学, 医学部, 准教授 (80305036)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大腸粘液癌 / オルガノイド / がん関連遺伝子

Outline of Final Research Achievements

Mucinous carcinoma, a subtype of colorectal adenocarcinoma, has a higher lymphatic invasion and poorer prognosis than conventional colorectal adenocarcinoma. We have reported that DUSP4 is a tumor suppressor gene involved in regulation of cell proliferation and invasion in conventional colorectal adenocarcinoma. On the other hand, increased expression of DUSP4 was observed in mucinous carcinoma, suggesting that its function is different from that in conventional colorectal adenocarcinoma. By downregulation of DUSP4 expression in a colorectal cancer cell line highly expressing DUSP4, the proliferation ability was significantly suppressed. From these findings, we hypothesized that DUSP4 functions as a tumor suppressor gene in normal colorectal adenocarcinoma, and as an oncogene in mucinous carcinoma. In this study, we attempted to establish mucinous cancer organoids to elucidate the pathogenesis of mucinous cancer.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

現在、公的細胞バンクには大腸粘液癌の形質を保持した細胞株がない。本研究では、患者検体から粘液癌のがんオルガノイドを樹立し、粘液癌の新規研究ツールとしての培養モデルを確立する。さらに、これらを用いて粘液癌の発症・進展に関わる分子メカニズムを解明する。本研究の成果は粘液癌の早期診断法や新規治療法の開発に役立ち、大腸癌全体の治療成績の向上に寄与することが期待される。