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

Journal: Journal of the American Society for Mass Spectrometry
Published Date:

Abstract

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.

Authors

  • Xuesen Hu
    State Key Laboratory of Medical Proteomics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • Tianrun Xu
    State Key Laboratory of Medical Proteomics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • Shengkai Xia
    Department of Respiratory Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
  • Yang Xu
    Dermatological Department, Nan Chong Center Hospital, Nanchong, China.
  • Yao Chen
    Department of Galactophore Surgery, West China Hospital, Sichuan University, Chengdu, 610041, PR China.
  • Liliang Wen
    State Key Laboratory of Medical Proteomics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • Wangshu Qin
    State Key Laboratory of Medical Proteomics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • Xianzhe Shi
    State Key Laboratory of Medical Proteomics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • Xinyu Liu
    Institute of Medical Technology, Peking University Health Science Center, Beijing, China.
  • Qi Wang
    Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Chunxiu Hu
    CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
  • Guowang Xu
    CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Keywords

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