The role of damage-associated molecules in organ-specific metastatic niche

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15522
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Shotaro Eto 東京大学, 先端科学技術研究センター, 特任研究員 (50940087)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: がん微小環境 / 転移ニッチ

Outline of Final Research Achievements

In this study, gene expression analysis of metastatic tumour cells and metastatic niche cells was performed to investigate tissue-specific metastatic niche formation mechanisms.
YAP/TAZ signalling was activated in lung metastatic cancer cells compared to the liver metastatic tumour cells. Inhibition of YAP/TAZ delayed tumour growth in the lung and increased peri-tumour CD8+ T cells.
Myeloid cells in liver metastases expressed high levels of Arg1. This phenomenon was also found to be synergistically induced by tumour cell-derived humoral factors and the hypoxic environment of the liver. Gene expression analysis of liver parenchymal cells around tumour cells also showed that a liver parenchymal regenerative response may be occurring around tumour cells.

Free Research Field

がん微小環境

Academic Significance and Societal Importance of the Research Achievements

本研究によって、臓器特異的な遺伝子発現やシグナル経路を同定することができた。これらを阻害する薬剤は、肺転移および肝転移特異的な治療法になりうる。がんの種類に依らない、転移が存在する解剖学的な”位置”に特異的な新規治療法開発のための足がかりとなる結果を得ることができたと考えている。またがん細胞周囲の肝実質細胞についてはほとんど研究がなされておらず、今後これらの活性化の意義を明らかにすることで、肝転移に特異的な治療法の開発につながると考えられる。