2020 Fiscal Year Final Research Report

Elucidation and application of early brain metastasis mechanism by Warburg regulator MPC

Research Project

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Project/Area Number	18K08704
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Osaka International Cancer Institute
Principal Investigator	KUDO Toshihiro 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 腫瘍内科副部長 (20593859)
Co-Investigator(Kenkyū-buntansha)	佐藤太郎大阪大学, 医学系研究科, 寄附講座教授 (40368303) 小関準大阪大学, 医学系研究科, 特任助教(常勤) (20616669) 坂井大介大阪大学, 医学部附属病院, 特任講師(常勤) (10621071) 石井秀始大阪大学, 医学系研究科, 特任教授(常勤) (10280736)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	化学療法 / 癌 / シングル細胞
Outline of Final Research Achievements	Brain metastases show strong treatment resistance, and the current situation is that current anticancer drugs, molecular-targeted therapies, and radiation therapy do not provide fundamental efficacy. Therefore, it is essential to elucidate the treatment resistance rooted in the true nature of cancer and to develop a treatment method. According to our research results, the regulation of anaerobic glycolysis by the key molecule MPC (mitochondrial pyruvate transporter) of the Warburg effect induces epithelial-mesenchymal transformation (EMT) to make cancer stem cells, and multiple It was revealed that the treatment resistance to the anticancer drug was acquired. For cancer cells that are relatively prone to brain metastasis as a mechanism, the role of MPC in early brain metastasis is investigated by single cells from the three-dimensional reconstruction of the cell group that constitutes the blood-brain barrier (BBB) toward the future clinical application.
Free Research Field	医学
Academic Significance and Societal Importance of the Research Achievements	より精密な診断のためのバイオマーカーの探索や、新たな治療標的を提示することができるようになり、がん代謝を介したMPCと細胞の形質転換の関連性を通じて、創薬の標的化、機序の解明、抵抗性の予測を通じて、難治がんの精密医療に貢献することができた。手術切除試料を用いた動物モデル(PDX: patient derived xenograft)と、三次元組織構築を構成する細胞群の解析から、早期の転移浸潤における責任分子の役割を究明し、創薬の標的化、機序の解明、抵抗性の予測を通じて、難治がんの精密医療に貢献することができた。