Elucidation of metabolointeractome in tumor microenvironments
| Project/Area Number |
21K19399
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Osawa Tsuyoshi 東京大学, 先端科学技術研究センター, 准教授 (50567592)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | がん / 代謝 / 細胞間相互作用 / アミノ酸 / オミクス統合解析 |
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| Outline of Research at the Start |
がんの転移・浸潤・薬剤耐性などの悪性化には腫瘍微小環境が重要な役割を果たす。申請者は、腫瘍微小環境において、分岐鎖アミノ酸のがん細胞への供給が、線維芽細胞や間質細胞からなされる新たなメカニズムが存在する可能性を見出している。本研究では、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する。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など、挑戦的な研究である。
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| 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.
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| 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
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] Metagenomic identification of microbial signatures predicting pancreatic cancer from a multinational study2022
Author(s)
Nagata N, Nishijima S, Kojima Y, Hisada Y, Imbe K, Miyoshi-Akiyama T, Suda W, Kimura M, Aoki R, Sekine K, Ohsugi M, Miki K, Osawa T, Ueki T, Oka S, Mizokami M, Kartal E, Schmidt TSB, Molina-Montes E, Estudillo L, Malats N, Trebicka J, Kersting S, Langheinrich M, Bork P, Uemura N, Itoi T, and Kawai T
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Journal Title
Gastroenterology
Volume: 163
Issue: 1
Pages: 222-238
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis2022
Author(s)
Murakami K, Sasaki Y, Asahiyama M, Yano W, Takizawa T, Kamiya W, Matsumura Y, Anai M, Osawa T, Fruchart JC, Fruchart-Najib J, Aburatani H, Sakai J, Kodama T, Tanaka T.
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Journal Title
Cells
Volume: 11
Issue: 4
Pages: 720-720
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever2021
Author(s)
Yoneshiro T, Kataoka N, Walejko JM, Ikeda K, Brown Z, Yoneshiro M, Crown SB, Osawa T, Sakai J, McGarrah RW, White PJ, Nakamura K, Kajimura S.
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DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] TET1 upregulation drives cancer cell growth through aberrant enhancer hydroxymethylation of HMGA2 in hepatocellular carcinoma.2021
Author(s)
Shirai K, Nagae G, Seki M, Kudo Y, Kamio A, Hayashi A, Okabe A, Ota S, Tsutsumi S, Fujita T, Yamamoto S, Nakaki R, Kanki Y, Osawa T, Midorikawa Y, Tateishi K, Ichinose M, Aburatani H.
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Journal Title
Cancer Sci.
Volume: 112
Issue: 7
Pages: 2855-2869
DOI
Related Report
Peer Reviewed / Open Access
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