{
  "abstract": "Background: Vascular invasion (VI) is an early event in breast cancer dissemination. However, the mechanisms by which macrophages and endothelial cells cooperate to drive this process remain incompletely understood. We aimed to identify macrophage subsets associated with VI and determine how they influence endothelial cell behavior.\n\nMethods: Single-cell RNA sequencing and spatial transcriptomic profiling and were conducted on breast cancer specimens partitioned by their vascular invasion characteristics. Multiplex immunofluorescence, coculture assays, transcriptomic, proteomic, and metabolomic profiling, molecular docking, and co-immunoprecipitation were used to characterize the SELENOP-LRP8 axis. In vivo validation was conducted using a myeloid-specific Selenop knockout model (Selenopf/f; Lyz2Cre) bearing E0771 allografts and treated with bevacizumab and/or Ebronucimab.\n\nResults: A distinct SELENOP+ macrophage subset was enriched in VI-positive breast tumors and exhibited close spatial proximity to endothelial cells. In vitro, macrophage-derived SELENOP enhanced endothelial migration and tube formation. Multi-omics analyses suggested that SELENOP binds endothelial LRP8, leading to cholesterol metabolic rewiring and Hedgehog pathway activation. In the mouse model, Selenop deficiency reduced tumor growth and vascularization, while combination treatment with bevacizumab and Ebronucimab produced the strongest inhibitory effect among the treatment groups.\n\nConclusions: These findings identify a SELENOP+ macrophage-endothelial metabolic axis associated with breast cancer VI and support further investigation of combined anti-angiogenic and cholesterol-pathway-directed strategies in preclinical models.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06359-y.",
  "abstract_shown": true,
  "affiliations": [
    "Department of tumor surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Haoran Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengdi Ran"
    },
    {
      "affs": [
        0
      ],
      "name": "Rui Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Weibo Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Oganezov Giorgi"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenxuan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tong Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Sheng Tai"
    },
    {
      "affs": [
        0
      ],
      "name": "Cheng Qian",
      "orcid": "0000-0001-8052-1006"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bhw2r6jsprqrc.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06359-y",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713971/",
  "id": "bhw2r6jsprqrc",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://doi.org/10.1007/s00018-026-06359-y",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
  ],
  "openalex": "W7172017904",
  "pdf_url": null,
  "pmcid": "PMC13713971",
  "pmid": "42946865",
  "published": "2026-07-31",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/bhw2r6jsprqrc.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:21:33Z",
      "native_id": "PMC13713971",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00018-026-06359-y"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Angiogenesis and VEGF in Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "SELENOP-LRP8-mediated macrophage-endothelial cell interaction promotes breast cancer vascular invasion by inducing metabolic reprogramming in endothelial cells",
  "title_text": "SELENOP-LRP8-mediated macrophage-endothelial cell interaction promotes breast cancer vascular invasion by inducing metabolic reprogramming in endothelial cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:33Z",
  "url": "https://research.draconitic.com/paper/bhw2r6jsprqrc",
  "venue": "Cellular and Molecular Life Sciences: CMLS",
  "versions": []
}