Molecular analysis of transdifferentiation in tumor tissue

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19468
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: YAO Ryoji 公益財団法人がん研究会, がん研究所 細胞生物部, 部長 (80291095)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 大腸癌 / 患者由来オルガノイド

Outline of Final Research Achievements

It is known that well- and moderately-differentiated tubular adenocarcinomas, which account for 90% of colorectal cancers, reflect the cellular lineage of normal colorectal tissues with stem cells at their apex. However, the mechanisms of development and homeostasis maintenance in poorly-differentiated colorectal cancers, which have different cellular compositions, are not well understood. In this study, we established patient-derived organoids and generated the analysis platform. Alongside gene mutation and expression analysis, we conducted single-cell level cloning and heterotopic and orthotopic transplantation experiments to investigate the differentiation conversion mechanisms of three types of poorly-differentiated colorectal cancer, including mucinous carcinoma, signet-ring cell carcinoma, and poorly-differentiated adenocarcinoma.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

複数の細胞種が存在する低分化大腸癌から患者由来オルガノイドを樹立することにより、がん組織の細胞多様性と可塑性の細胞生物学的な解析が可能になったことは、学術的に意義があると考えられる。また、進行が早く、腹膜転移が多いとされ、予後不良であることが知られている低分化大腸癌の治療法開発の解析プラットフォームとしての貢献が期待される。