{
  "abstract": "Progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) marks a critical step in breast cancer progression, yet the mechanisms governing this transition remain poorly defined. Here, we identify neutrophils as a key immunological driver of DCIS progression. Across two independent breast cancer mouse models, neutrophil depletion or genetic deletion of their tumor-derived chemoattractant chitinase-3 like 1 (Chi3l1) preserves the myoepithelial barrier, halts DCIS-to-IDC transition, and suppresses lung metastasis. Mechanistically, tumor-infiltrating neutrophils release neutrophil elastase (NE) that degrades the basement membrane extracellular matrix, leading to erosion of the myoepithelial layer by anoikis. Pharmacological NE inhibition restores myoepithelial integrity and blocks DCIS progression and metastasis. Consistently, elevated NE levels in human breast cancer samples are associated with myoepithelial disruption, DCIS progression, and metastasis. Together, these findings identify neutrophils as key mediators of myoepithelial barrier disruption and highlight NE as a potential therapeutic target for high-risk DCIS.",
  "abstract_shown": true,
  "affiliations": [
    "McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, QC H4A 3J1, Canada",
    "Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada",
    "McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, QC H3A 1A3, Canada",
    "Department of Surgery, Division of Surgical and Interventional Sciences, McGill University, Montreal, QC H3G 1A4, Canada",
    "Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tarek Taifour"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yu Gu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Adéline Massé"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Xiwei Meng"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Clarisse Dane Echavez"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongmei Zuo"
    },
    {
      "affs": [
        1
      ],
      "name": "Virginie Sanguin-Gendreau"
    },
    {
      "affs": [
        1
      ],
      "name": "Anne Blouin"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Adda-Lee Graham-Paquin"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Miranda Addie"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Emilie Solymoss"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Xiao"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Hailey Proud"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sherif Samer Attalla"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Alice Jisoo Nam"
    },
    {
      "affs": [
        1
      ],
      "name": "Vasilios Papavasiliou"
    },
    {
      "affs": [
        1
      ],
      "name": "Hellen Kuasne"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Peter M. Siegel"
    },
    {
      "affs": [
        4
      ],
      "name": "Khandan Keyomarsi"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Luke McCaffrey"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Morag Park"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "William J. Muller"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5eap9vf2pt7hk.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103050",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710378/",
  "id": "5eap9vf2pt7hk",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103050",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7212287999",
  "pdf_url": null,
  "pmcid": "PMC13710378",
  "pmid": "42727582",
  "published": "2026-09-11",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/5eap9vf2pt7hk.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:21Z",
      "native_id": "PMC13710378",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103050"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Neutrophil elastase-mediated myoepithelial loss is a therapeutic vulnerability in ductal carcinoma in situ progression",
  "title_text": "Neutrophil elastase-mediated myoepithelial loss is a therapeutic vulnerability in ductal carcinoma in situ progression",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:21Z",
  "url": "https://research.draconitic.com/paper/5eap9vf2pt7hk",
  "venue": "Cell Reports Medicine",
  "versions": []
}