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Peer-reviewedCC BY 4.0Cell Reports Medicine

Neutrophil elastase-mediated myoepithelial loss is a therapeutic vulnerability in ductal carcinoma in situ progression

  • Tarek Taifour1,2
  • Yu Gu2,3
  • Adéline Massé2,3
  • Xiwei Meng2,3
  • Clarisse Dane Echavez2,3
  • Dongmei Zuo2
  • Virginie Sanguin-Gendreau2
  • Anne Blouin2
  • Adda-Lee Graham-Paquin2,3
  • Miranda Addie2,4
  • Emilie Solymoss1,2
  • Bin Xiao2
10 more authors
  • Hailey Proud2,3
  • Sherif Samer Attalla2,3
  • Alice Jisoo Nam2,3
  • Vasilios Papavasiliou2
  • Hellen Kuasne2
  • Peter M. Siegel1,2,3
  • Khandan Keyomarsi5
  • Luke McCaffrey1,2,3
  • Morag Park1,2,3
  • William J. Muller1,2,3
5 affiliations
  1. 1McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, QC H4A 3J1, Canada
  2. 2Rosalind and Morris Goodman Cancer Institute, Montreal, QC H3A 1A3, Canada
  3. 3McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, QC H3A 1A3, Canada
  4. 4Department of Surgery, Division of Surgical and Interventional Sciences, McGill University, Montreal, QC H3G 1A4, Canada
  5. 5Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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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.

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Cite

BibTeXRIS
BibTeX
@article{taifour2026neutrophil,
  title = {{Neutrophil elastase-mediated myoepithelial loss is a therapeutic vulnerability in ductal carcinoma in situ progression}},
  author = {Tarek Taifour and Yu Gu and Adéline Massé and Xiwei Meng and Clarisse Dane Echavez and Dongmei Zuo and Virginie Sanguin-Gendreau and Anne Blouin and Adda-Lee Graham-Paquin and Miranda Addie and Emilie Solymoss and Bin Xiao and Hailey Proud and Sherif Samer Attalla and Alice Jisoo Nam and Vasilios Papavasiliou and Hellen Kuasne and Peter M. Siegel and Khandan Keyomarsi and Luke McCaffrey and Morag Park and William J. Muller},
  journal = {Cell Reports Medicine},
  year = {2026},
  month = sep,
  doi = {10.1016/j.xcrm.2026.103050},
  url = {https://doi.org/10.1016/j.xcrm.2026.103050},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Neutrophil elastase-mediated myoepithelial loss is a therapeutic vulnerability in ductal carcinoma in situ progression
AU  - Tarek Taifour
AU  - Yu Gu
AU  - Adéline Massé
AU  - Xiwei Meng
AU  - Clarisse Dane Echavez
AU  - Dongmei Zuo
AU  - Virginie Sanguin-Gendreau
AU  - Anne Blouin
AU  - Adda-Lee Graham-Paquin
AU  - Miranda Addie
AU  - Emilie Solymoss
AU  - Bin Xiao
AU  - Hailey Proud
AU  - Sherif Samer Attalla
AU  - Alice Jisoo Nam
AU  - Vasilios Papavasiliou
AU  - Hellen Kuasne
AU  - Peter M. Siegel
AU  - Khandan Keyomarsi
AU  - Luke McCaffrey
AU  - Morag Park
AU  - William J. Muller
PY  - 2026
DA  - 2026/09/11
JO  - Cell Reports Medicine
DO  - 10.1016/j.xcrm.2026.103050
UR  - https://doi.org/10.1016/j.xcrm.2026.103050
AB  - 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.
SN  - 2666-3791
ER  -