Metabolic analysis of tongue cancer to develop new therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16329
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Murakami Shoko 滋賀医科大学, 医学部, 医師(非常勤) (50773975)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: がん代謝 / 舌がん / 3次元培養

Outline of Final Research Achievements

To elucidate the metabolism of tongue cancer, we performed comprehensive metabolic analysis in three groups: a conventional 2D culture group (2D), a 3D culture group using a novel 3D culture system, a “tissueoid cell culture system” (3D), and a xenograft group in which tongue cancer cells were xenografted into nude mice. The results showed that tongue cancer metabolism differed significantly between 2D and 3D; many metabolites in 3D were similar to those in xenografts; mitochondrial function was not impaired in 3D, and metabolic reprogramming occurred to promote cell proliferation in 3D and xenografts. On the other hand, 2D underwent specialized metabolism to survive under conditions different from those in vivo. Metabolic analysis of 3D, which can mimic the morphology and function of living cancer tissue, yielded results consistent with previously reported theories of cancer metabolism.

Free Research Field

腫瘍生物学関連

Academic Significance and Societal Importance of the Research Achievements

3D とxenograftでは、がん細胞は、グルコースなどの栄養素を用いて解糖系やクエン酸回路を活発に利用することにより、バイオマスの生合成と酸化的リン酸化によるエネルギー産生、酸化還元バランスの維持を行っていることが明らかとなった。本3D培養系は形態だけでなく、機能的にもバイオマス生合成とエネルギー産生の面で、生体に近い状態を再現できた。本3D培養系は極めて新規性の高い、がん研究において重要な実験ツールであると考えられた。今後は本3D培養系を応用して抗がん剤のターゲットとなりうるがん代謝関連酵素の同定が期待できる。