Study of the metastatic process in a mouse model transplanted with the organoids derived from human colorectal cancer.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: YAGINUMA Katsuyuki 公益財団法人がん研究会, がん研究所 細胞生物部, 研究員 (40182307)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 大腸がん / 転移モデルマウス / 患者由来オルガノイド / 播種腫瘍細胞 / 腫瘍幹細胞 / EMT

Outline of Final Research Achievements

To study the metastatic process, we established a mouse model orthotopically- transplanted with the organoids (PDOs) derived from primary, metastatic, recurrent tumors of the same patient. Although these mice developed colorectal tumors equally, lung metastasis was frequently observed in mice with PDO from the recurrent tumor. On the other hand, any macroscopic metastasis was not observed in mice with PDO from the primary tumor, suggesting that PDO from the recurrent tumor has higher metastatic ability than PDO from the primary tumor. We also focused on the expression of EMT markers, which is implicated in tumor cell invasion and metastasis.Furthermore, we successfully established the novel organoids originated from the disseminated cells in remote organs, which are assumed to be an intermediate state in the metastatic process and demonstrated the occurrence of lung metastasis by transplantation of these novel organoids even in a low incidence.

Free Research Field

実験腫瘍学

Academic Significance and Societal Importance of the Research Achievements

大腸がんの転移モデルマウスとしては脾内移植や尾静脈などの異所移植があるが、これは転移プロセスの一部分だけを再現した方法であり、申請者らが構築した、大腸への同所移植による転移モデルマウス実験系は、より生理的に全体を再現する方法として優れている。このモデルマウスを用いることで、ヒト大腸がんの原発巣と転移巣の腫瘍細胞の多様性と階層性の解析が可能になり、さらに、播種腫瘍細胞由来のオルガノイドを分離できたことは、転移プロセスの詳細な分子メカニズムの解明に繋がるとともに、転移抑制の治療法の選択や予後予測の精度の向上が期待される。