Exploring novel mechanisms of chemotherapy-induced metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07659
• 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: Kansai Medical University (2021-2022); Kanazawa University (2020); The University of Tokyo (2019)
• Principal Investigator: SAKAMOTO Takeharu 関西医科大学, 医学部, 教授 (70511418)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 転移 / 化学療法

Outline of Final Research Achievements

It has been reported that chemotherapy using cytotoxic anticancer agents may rather promote cancer metastasis, but the detailed mechanism is unknown. In this study, we focused on the molecule Mint3, which is known to promote cancer metastasis in macrophages, and analyzed chemotherapy-induced metastasis using Mint3-deficient mice. The results showed that chemotherapy-induced metastasis was suppressed in Mint3-deficient mice. Further analysis revealed that chemotherapy-induced metastasis is induced by Mint3-dependent induction of Molecule X expression in alveolar type II epithelial cells by chemotherapy-activated macrophages, and that Molecule X promotes cancer cell metastasis.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、詳細が不明であった化学療法誘導性転移の分子メカニズムの一端が明らかとなった。特に、マクロファージ―肺胞II型上皮細胞―がん細胞の細胞間相互作用が、肺への化学療法誘導性転移に関わることは、臓器特異性をもった化学療法誘導性転移機構があることを解明した点で学術的に重要な発見である。また、Mint3や分子Xを阻害することで化学療法誘導性転移が抑制されることから、術前化学療法時にこれら分子の阻害剤を併用することで、化学療法誘導性転移のリスクを下げる可能性があるため、今後の臨床応用に向けて社会的意義のある研究成果である。