{
  "abstract": "Bone metastasis can be facilitated by systemic remodeling, yet the tumor‐derived signals that influence the bone marrow microenvironment remain incompletely understood. Large oncosomes (LOs) are atypically large (> 1 µm), tumor‐derived extracellular vesicles shed by amoeboid cancer cells. Here, we demonstrate that LOs function as systemic mediators of metastatic niche formation by activating innate immune sensing in bone marrow mesenchymal stem cells (BM‐MSCs). Systemic administration of LOs to immunocompetent tumor‐bearing mice did not affect primary tumor growth but increased metastatic burden. LOs induced a robust, dose‐dependent interferon‐driven inflammatory program, characterized by interferon‐stimulated genes and neutrophil chemokines. Mechanistically, this response was driven by LO‐associated nucleic acids activating convergent cytosolic DNA‐ and RNA‐sensing pathways in recipient stromal cells. LO‐conditioned BM‐MSCs promoted the accumulation and polarization of neutrophils toward an immunosuppressive, polymorphonuclear myeloid‐derived suppressor cell (PMN‐MDSC)‐like phenotype. In vivo, genetic suppression of LO shedding in tumor cells reduced PMN‐MDSC accumulation in the bone marrow, which was reversed by systemic LO administration. Together, these findings support a model in which LO‐associated signals reprogram the bone marrow microenvironment to support metastatic colonization, identifying a previously unrecognized mechanism linking tumor vesiculation to immune remodeling at distant sites.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology Cedars‐Sinai Health Sciences University Los Angeles California USA",
    "Department of Medicine Cedars‐Sinai Health Sciences University Los Angeles California USA",
    "Department of Biomedical Sciences Cedars‐Sinai Health Sciences University Los Angeles California USA",
    "Department of Orthopaedics Cedars‐Sinai Health Sciences University Los Angeles California USA",
    "Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II Naples Italy",
    "Department of Radiation Oncology Cedars‐Sinai Health Sciences University Los Angeles California USA",
    "Department of Genetics University of Texas MD Anderson Cancer Center Houston Texas USA",
    "Department of Radiological, Oncological and Pathological Sciences Sapienza University of Rome Rome Italy"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Taylon Felipe Silva",
      "orcid": "0000-0003-3491-2828"
    },
    {
      "affs": [
        0
      ],
      "name": "Virginia Marcia Concato‐Lopes",
      "orcid": "0000-0001-5451-6254"
    },
    {
      "affs": [
        0
      ],
      "name": "Fatima Bedier"
    },
    {
      "affs": [
        0
      ],
      "name": "Lauren Newman",
      "orcid": "0000-0003-3303-1666"
    },
    {
      "affs": [
        0
      ],
      "name": "Diana Kitka",
      "orcid": "0000-0002-8319-5960"
    },
    {
      "affs": [
        0
      ],
      "name": "Jamelle Brown",
      "orcid": "0000-0002-2040-0488"
    },
    {
      "affs": [
        0
      ],
      "name": "Blandine Victor"
    },
    {
      "affs": [
        0
      ],
      "name": "Minhyung Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Tatyana Vagner"
    },
    {
      "affs": [
        1
      ],
      "name": "Catherine Grasso"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Dmitriy Sheyn",
      "orcid": "0000-0002-3333-1485"
    },
    {
      "affs": [
        0
      ],
      "name": "Sungyong You",
      "orcid": "0000-0003-3513-1783"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Michael R. Freeman"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Fayyaz S. Sutterwala",
      "orcid": "0000-0002-7338-3095"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Helen S. Goodridge",
      "orcid": "0000-0001-8097-2413"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Caroline Jefferies"
    },
    {
      "affs": [
        4
      ],
      "name": "Paola de Candia",
      "orcid": "0000-0003-4767-446X"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Jlenia Guarnerio",
      "orcid": "0000-0001-7576-7095"
    },
    {
      "affs": [
        0,
        2,
        7
      ],
      "name": "Dolores Di Vizio",
      "orcid": "0000-0002-9787-6556"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fzdymfedhmp62.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78406",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696780/",
  "id": "fzdymfedhmp62",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78406",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7223556235",
  "pdf_url": "https://europepmc.org/articles/PMC13696780?pdf=render",
  "pmcid": "PMC13696780",
  "pmid": "42928450",
  "published": "2026-10-25",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/fzdymfedhmp62.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:04Z",
      "native_id": "PMC13696780",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78406"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928450",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928450"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Large Oncosomes Induce Pro‐Metastatic Stromal‐Myeloid Reprogramming",
  "title_text": "Large Oncosomes Induce Pro‐Metastatic Stromal‐Myeloid Reprogramming",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:03Z",
  "url": "https://research.draconitic.com/paper/fzdymfedhmp62",
  "venue": "Advanced Science",
  "versions": []
}