Elucidation of Warburg effect induced by cancer-associated fibroblasts

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K14999
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Ohnishi Naomi 公益財団法人がん研究会, がんプレシジョン医療研究センター がんオーダーメイド医療開発プロジェクト, 研究員 (50507217)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: エクソソーム / 腎癌 / ワールブルグ効果

Outline of Final Research Achievements

Metabolic shifts (Warburg effect) are known to occur in cancer, but little is known about their significance or molecular mechanisms. Recently, from the analysis of exosomes secreted from human cancer specimens, we hypothesized that cancer-associated fibroblasts (CAF) in the renal cancer microenvironment provide a continuous and abundant supply of glycogen to cancer cells via exosomes. In this study, we first constructed a method to efficiently isolate and culture CAF from human kidney cancer tissues. In addition, we measured the amount of glycogen delivered to cancer cells by CAF-derived exosomes, and quantitatively analyzed the amount of each flux together with the amount of metabolite change induced in cancer cells to clarify the whole picture of the Warburg effect.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究は、90年以上前から現象として知られてきたワールブルグ効果の分子機序をエクソソームを介した癌-間質間相互作用の観点から解明しようという新しい試みである。本研究から得られた成果は、多くの癌で特徴的に認められるワールブルグ効果がどのようにグルコースを獲得しどのような代謝経路によって癌の増殖を支持するかを明らかにするものであり、CAF由来エクソソームならびに癌特異的代謝機構を標的とした広い癌種に適用可能な癌治療薬開発に繋がる可能性がある。