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*,
{"title":"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。","authors":"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*, ","doi":"10.1021/jasms.5c00177","DOIUrl":null,"url":null,"abstract":"<p >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.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 9","pages":"1959–1969"},"PeriodicalIF":2.7000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metabolic Adaptation Study of Tumor Cells during Lung Cancer Bone Metastasis in Mice Based on Single-Cell Metabolome Analysis\",\"authors\":\"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*, \",\"doi\":\"10.1021/jasms.5c00177\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Lung cancer metastasis, the leading cause of patient mortality, is driven by circulating tumor cells (CTCs), which act as direct mediators of metastatic spread. 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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.
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