Dissection of molecular mechanisms of the metastatic niche dormancy and application to the ant-metastatic therapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15625
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Juntendo University
• Principal Investigator: kojima yutaka 順天堂大学, 医学部, 准教授 (00327800)
• Co-Investigator(Kenkyū-buntansha): 小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982) ; 折茂 彰 順天堂大学, 医学(系)研究科(研究院), 准教授 (70275866)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: metastatic dormancy / CAFs / tumor microenvironment

Outline of Final Research Achievements

Our previous findings demonstrated that CAFs promote tumor malignancy of nearby carcinoma cells. We here aimed to determine whether CAFs also regulate the niche for metastatic dormancy to boost metastasis. To do so, we checked roles of CAFs on metastatic ability of tumor organoids generated from human colon carcinomas. We found that CAFs boost tumor metastasis of colon tumor organoids in the liver and lungs significantly more than did control fibroblasts did, when orthotopically injected into immunodeficient mice. These findings indicate that CAFs may play roles for niches to activate metastatic dormancy, however, more clear evidences await future study.

Free Research Field

癌生物学

Academic Significance and Societal Importance of the Research Achievements

癌死亡の９０％は転移再発に起因している。癌診断時に臨床的に転移が認められないが、原発巣治療後数年以内に転移再発で命を落とす患者数は少なくない。転移再発は、遠隔臓器の新しい環境に適応できず細胞増殖を停止している(dormant)癌細胞の再増殖に依存している。もし癌細胞のdormancyを制御機構を解明し臨床に応用することができれば、転移癌細胞との共存が可能になるかもしれない。