基于单细胞代谢组学分析的小鼠肺癌骨转移过程中肿瘤细胞代谢适应研究。

IF 2.7 2区 化学 Q2 BIOCHEMICAL RESEARCH METHODS
Xuesen Hu, Tianrun Xu, Shengkai Xia, Yang Xu, Yao Chen, Liliang Wen, Wangshu Qin, Xianzhe Shi, Xinyu Liu, Qi Wang*, Chunxiu Hu* and Guowang Xu*, 
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引用次数: 0

摘要

肺癌转移是患者死亡的主要原因,它是由循环肿瘤细胞(ctc)驱动的,它是转移扩散的直接介质。为了阐明肺癌转移阶段的代谢异质性,利用纳米电喷雾电离-大气压化学电离源对小鼠肺癌骨转移模型进行了全景单细胞代谢组学研究。该平台能够实现极性和非极性代谢物的高覆盖率检测,克服了灵敏度和代谢物多样性的限制。单细胞代谢谱的无监督聚类和降维(t-SNE)区分了原发肿瘤细胞、CTCs和骨转移细胞,揭示了特定阶段的代谢重编程。机器学习识别出关键代谢物(例如,氨基苯甲酸、2-甲基-3-酮戊酸、泛酸),这些代谢物能够以高精度(AUC > 0.96)强有力地区分转移阶段。ctc在不同阶段表现出动态的代谢适应:在血液循环过程中,氨基酸和谷氨酰胺代谢主导以抵消营养剥夺,而在骨定植过程中,三羧酸循环和单碳代谢上调以支持增殖。本研究为揭示肿瘤细胞的代谢异质性和肺癌的转移机制提供了重要数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Metabolic Adaptation Study of Tumor Cells during Lung Cancer Bone Metastasis in Mice Based on Single-Cell Metabolome Analysis

Metabolic Adaptation Study of Tumor Cells during Lung Cancer Bone Metastasis in Mice Based on Single-Cell Metabolome Analysis

Lung cancer metastasis, the leading cause of patient mortality, is driven by circulating tumor cells (CTCs), which act as direct mediators of metastatic spread. To elucidate the metabolic heterogeneity across lung cancer metastatic stages, a panoramic single-cell metabolomics study in a mouse lung cancer bone metastasis model was performed using a concentric hybrid nanoelectrospray ionization-atmospheric pressure chemical ionization source. This platform enables high-coverage detection of polar and nonpolar metabolites, overcoming limitations in sensitivity and metabolite diversity. Unsupervised clustering and dimensionality reduction (t-SNE) of single-cell metabolic profiles distinguished primary tumor cells, CTCs, and bone metastatic cells, revealing stage-specific metabolic reprogramming. Machine learning identified key metabolites (e.g., aminobenzoic acid, 2-methyl-3-ketovaleric acid, pantothenic acid) that robustly discriminated metastatic stages with high accuracy (AUC > 0.96). CTCs exhibited dynamic metabolic adaptions at different stages: during blood circulation, amino acid and glutamine metabolism dominated to counteract nutrient deprivation, while during bone colonization, the tricarboxylic acid cycle and one-carbon metabolism were upregulated to support proliferation. This study provides important data to shed light on the metabolic heterogeneity of tumor cells and the metastasis mechanism of lung cancer.

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来源期刊
CiteScore
5.50
自引率
9.40%
发文量
257
审稿时长
1 months
期刊介绍: The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role. Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives
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