Identification of slow-cycling colon cancer stem cells by single cell gene expression analysis of chemoresistant cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16230
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Teikyo University (2022); National Cancer Center Japan (2020-2021)
• Principal Investigator: Kanda Yusuke 帝京大学, 先端総合研究機構, 研究員 (80803949)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 抗がん剤抵抗性 / 大腸がん

Outline of Final Research Achievements

Recently, a small group of slow-cycling cancer cells has been reported to be resistant to anticancer drugs, but the presence of the population in colon cancer is unknown. To prove the existence of slow-cycling cancer stem cells in colon cancer, we introduced induced H2B-EGFP into organoids established from colon cancer patients. We found that H2B-EGFP-positive cells are chemoresistant and that signature genes of H2B-EGFP-positive cells. In vitro system for gene KO was established. Next, we examined the presence of dormant cancer cells in the xenograft tumor. Colon cancer organoids were transplanted into immunodeficient mice, and H2B-EGFP expression was induced for a certain period, followed by administration of Irinotecan. As a result, we found that H2B-EGFP-positive cancer cells remained.

Free Research Field

がん

Academic Significance and Societal Importance of the Research Achievements

休止型がん幹細胞は、抗がん剤抵抗性の要因であると考えられている。本研究で得られた成果は、ヒト大腸がん組織内に休止型がん幹細胞を見出したものであり、今後、休止型大腸がん幹細胞を標的とした治療法の開発が期待される。