Elucidation of metabolointeractome in tumor microenvironments

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19399
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Osawa Tsuyoshi 東京大学, 先端科学技術研究センター, 准教授 (50567592)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: がん / 代謝 / 細胞間相互作用 / アミノ酸 / オミクス統合解析

Outline of Final Research Achievements

The tumor microenvironment plays an important role in malignant tumor such as metastasis, invasion, and drug resistance. In this research we found a novel mechanism by which branched-chain amino acids are supplied to cancer cells from fibroblasts and stromal cells in the tumor microenvironment. In addition, we found amino acids as key metabolic interaction between cancer and fibroblast (metabolo-interactome) in tumor tissues evaluated by following two research topics: (1) exploration of key cell-cell interactions in the tumor microenvironment and (2) elucidation of the metabolic interactions within tumor microenvironment. We have identified potential nutrient sensing/regulation factors that may lead to the development of novel cancer therapies, and have also elucidated a novel nutrient supply mechanism in tumor.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、アミノ酸を軸とした腫瘍組織における細胞間相互作用で鍵となる代謝物（メタボロインタラクト―ム）の探索的な研究から新規がんの治療法の開発につながる研究を目的とした。本研究は、がん研究のみならず、アミノ酸代謝疾患研究、栄養学研究、mTOR研究などの学術体系の変革や転換にも繋がる可能性を有し、がんを克服する画期的な代謝疾患の制御法を開発に繋がる研究である。また、本研究は、申請者が持つ独自のアミノ酸培養系で、これまで他の栄養素の作用が混在し解析が困難であった１代謝物に起因する系統的な多階層オミクス解析で実現し、がん細胞の生存や幹細胞性維持や腫瘍組織の細胞間相互作用の鍵代謝物の同定に繋がった