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超极化[1-C]丙酮酸核磁共振波谱揭示了微尺度多细胞球体中肿瘤能量代谢的转变。

Hyperpolarized [1-C]pyruvate NMR spectroscopy reveals transition of tumor energy metabolism in microscale multicellular spheroids.

作者信息

Takakusagi Yoichi, Takakusagi Kaori, Inoue Kaori, Saito Keita, Homma Yoshimi, Ichikawa Kazuhiro

机构信息

Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan.

Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science (iQMS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan.

出版信息

Sci Rep. 2025 Jun 2;15(1):19303. doi: 10.1038/s41598-025-03454-1.

DOI:10.1038/s41598-025-03454-1
PMID:40456829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12130504/
Abstract

Hyperpolarized (HP) [1-C]pyruvate nuclear magnetic resonance (NMR) spectroscopy was employed to investigate tumor energy metabolism in microscale multicellular spheroids of a few hundred micrometers in diameter, serving as a model of early-phase tumorigenesis in vivo. A three-dimensional static culture of murine squamous cell carcinoma (SCCVII) cells formed uniform smaller multicellular spheroids (~ 150 μm in diameter), without hypoxic or necrotic cores, yet these spheroids exhibited resistance to anti-tumor drugs. HP [1-C]pyruvate NMR spectroscopy of SCCVII spheroids revealed an increased conversion of pyruvate to lactate compared to monolayer cultures, indicating enhanced aerobic glycolysis in the aggregated cells. Additionally, HP spectroscopy differentiated the degree of aerobic glycolysis in human prostate tumor spheroids-DU145 (~ 120 μm) and PC-3 (~ 230 μm)-as evidenced by the upregulation of genes associated with lactate production and cellular transport. The Lac/Pyr ratio among spheroids correlated with those observed in homogenate samples of corresponding tumors grown in mice. These findings suggest that HP [1-C]pyruvate NMR spectroscopy may serve as a metabolic biomarker for early-phase tumorigenesis in vivo.

摘要

采用超极化(HP)[1 - C]丙酮酸核磁共振(NMR)光谱技术,对直径几百微米的微尺度多细胞球体中的肿瘤能量代谢进行研究,该球体作为体内早期肿瘤发生的模型。小鼠鳞状细胞癌(SCCVII)细胞的三维静态培养形成了均匀的较小多细胞球体(直径约150μm),没有缺氧或坏死核心,但这些球体表现出对抗肿瘤药物的抗性。SCCVII球体的HP [1 - C]丙酮酸NMR光谱显示,与单层培养相比,丙酮酸向乳酸的转化增加,表明聚集细胞中的有氧糖酵解增强。此外,HP光谱区分了人前列腺肿瘤球体 - DU145(约120μm)和PC - 3(约230μm)中的有氧糖酵解程度,这由与乳酸产生和细胞转运相关的基因上调所证明。球体中的Lac/Pyr比值与在小鼠体内生长的相应肿瘤匀浆样品中观察到的比值相关。这些发现表明,HP [1 - C]丙酮酸NMR光谱可能作为体内早期肿瘤发生的代谢生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/45e53a0c904d/41598_2025_3454_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/75ec1c08991a/41598_2025_3454_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/caa291b6ae6d/41598_2025_3454_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/2f78b9b08cc5/41598_2025_3454_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/1ac2bd2f828e/41598_2025_3454_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/45e53a0c904d/41598_2025_3454_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/75ec1c08991a/41598_2025_3454_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/caa291b6ae6d/41598_2025_3454_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/2f78b9b08cc5/41598_2025_3454_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/1ac2bd2f828e/41598_2025_3454_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad5c/12130504/45e53a0c904d/41598_2025_3454_Fig5_HTML.jpg

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