Inflammatory and fibrotic microenvironment in promotion of liver metastasis of colon cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03498
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kanazawa University
• Principal Investigator: Oshima Hiroko 金沢大学, がん進展制御研究所, 准教授 (80362515)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大腸がん / 転移 / 微小環境 / 線維化 / オルガノイド

Outline of Final Research Achievements

In this project, we have studied the role of inflammatory and fibrotic microenvironment in the liver metastasis of intestinal tumor cells. For this purpose, we have established mouse intestinal tumor-derived organoids carrying major driver mutations of colon cancer, and generated liver metastasis models by transplantation of these organoids to the spleen. We found that fibrotic microenvironment was generated surrounding the disseminated tumor cells by activation of hepatic stellate cells, which support survival and proliferation of the disseminated tumor cells, leading to development of metastatic foci. Moreover, we found that host TGF-β signaling is required for generation of fibrotic niche and development of metastatic foci in the liver. Moreover, host innate immune response and inflammatory pathway also contributed to the metastatic foci formation. These results expand our knowledge about the role of microenvironment in colon cancer metastasis.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

発がん過程における炎症性微小環境の役割について研究が進み、発がん予防戦略に重要な知見を与えている。一方で、転移などの悪性化進展過程における微小環境については、未だ不明な点が多い。本研究では、腸管腫瘍の肝転移過程における線維性微小環境の役割に着目し、ヒト大腸がん細胞の遺伝子変異を再現したマウスオルガノイドの移植モデルを用いて、線維性微小環境の形成機構とその重要性について明らかにした。以上の研究成果は、転移巣形成機構の理解を広げ、将来的な転移がんに対する治療戦略にも貢献が期待される。