{
  "abstract": "Background\n\nBreast cancer is a highly common malignancy in women, with bone as its most frequent site of distant metastasis significantly increasing mortality risk.Methods\n\nThis study integrated single-cell RNA sequencing datasets (GSE266330 and GSE243526) to systematically characterize the tumor microenvironment across normal tissue, primary tumor, and bone metastasis in breast cancer.Results\n\nIn total, 141 056 high-quality single cells were analyzed from an integrated cohort comprising a bone-metastasis dataset (GSE266330) and a primary/normal breast dataset (GSE243526), identifying 11 major cell types. Within the bone-metastatic cohort, we identified a macrophage subpopulation highly expressing SPP1 (Mac-SPP1) that exhibited an M2-polarized signature and elevated metabolic gene-set enrichment, and that expressed transcription factors such as HOXA9 and MAF. We also identified CD4-S100A9 and CD8-GZMK T-cell subpopulations with high cytotoxicity, high exhaustion, and metabolic reprogramming. Pseudotime analysis positioned CD4-S100A9 cells at one end of the inferred CD4+ T-cell trajectory and CD8-GZMK cells at an intermediate node along the inferred CD8+ T-cell trajectory. Cell-cell communication analysis predicted that Mac-SPP1 interacts with these T-cell subsets through the SPP1-integrin (e.g., SPP1-CD44) and CD74-MIF/COPA signaling axes.Conclusion\n\nThis study provides a single-cell characterization of the breast cancer bone-metastatic microenvironment, identifying an SPP1-expressing macrophage subset (Mac-SPP1) and predicting its interactions with CD4-S100A9 and CD8-GZMK T cells. Because the bone-metastatic and primary/normal specimens derive from different datasets, these findings are descriptive and cannot be attributed to metastatic progression alone and require experimental validation and confirmation in cohorts that profile primary and metastatic specimens within a single study.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, Zhejiang Provincial People's Hospital Bijie Hospital (The First People's Hospital of Bijie), Bijie, Guizhou, China.",
    "Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.",
    "Hangzhou Medical College, Hangzhou, Zhejiang, China.",
    "Department of Orthopedics, Zhejiang Provincial People's Hospital Bijie Hospital (The First People's Hospital of Bijie), Bijie, Guizhou, China.",
    "Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.",
    "Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Zixue Xuan",
      "orcid": "0000-0002-6296-4062"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongxiu Wu",
      "orcid": "0009-0007-0435-7348"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuting Zhong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jinying Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lei Cheng",
      "orcid": "0000-0002-3555-5116"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Jun Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Kai Wang",
      "orcid": "0000-0003-4529-2134"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ef5atvhtsqkrc.bib",
  "cited_by": 0,
  "doi": "10.1002/cnr2.70732",
  "fulltext_url": "https://europepmc.org/articles/PMC13724617",
  "id": "ef5atvhtsqkrc",
  "issns": [
    "2573-8348"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968173",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7133500372",
  "pdf_url": "https://europepmc.org/articles/PMC13724617?pdf=render",
  "pmcid": "PMC13724617",
  "pmid": "42968173",
  "published": "2026-11-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/ef5atvhtsqkrc.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42968173",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968173"
    },
    {
      "first_seen": "2026-11-04T12:23:09Z",
      "native_id": "PMC13724617",
      "source": "pmc",
      "url": "https://doi.org/10.1002/cnr2.70732"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Single-Cell Characterization of SPP1-Expressing Macrophages and Their Predicted Interactions With T Cells in the Breast Cancer Bone Metastatic Microenvironment.",
  "title_text": "Single-Cell Characterization of SPP1-Expressing Macrophages and Their Predicted Interactions With T Cells in the Breast Cancer Bone Metastatic Microenvironment.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:03Z",
  "url": "https://research.draconitic.com/paper/ef5atvhtsqkrc",
  "venue": "Cancer reports (Hoboken, N.J.)",
  "versions": []
}