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Peer-reviewedCC BY-NC-ND 4.0BMC Biology

Transcriptomic insights into age-associated extracellular matrix promotion of breast cancer

  • Lauren Hawthorne1,2
  • Gokhan Bahcecioglu1,2
  • Jun Yang3
  • Emilija Aleksandrovic4
  • Erin Howe5
  • Siyuan Zhang4
  • Pinar Zorlutuna1,2,3
5 affiliations
  1. 1Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556 USA
  2. 2Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556 USA
  3. 3Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556 USA
  4. 4Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
  5. 5Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, IL 60064 USA
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Abstract

Background: Aging is a key risk factor for breast cancer; however, the independent effects of the aged extracellular matrix (ECM) remain understudied.

Results: To address this, we developed a novel hybrid in vivo model that enables the independent investigation of age-related ECM influences on breast cancer development and progression. To examine the effects of genes known to be enriched in a cancerous and aged microenvironment, we first seeded normal or stable knockdown cells onto decellularized ECM (dECM) from aged murine mammary glands and implanted them into young Rag1−/− mice. We identified LOX as a principal driver of tumor progression, with knockdown reducing invasion, in vitro and in vivo, and stress-related pathways. To further isolate the independent influence of ECM aging on tumor growth, normal MCF10A cells were seeded atop young or aged matrices and implanted. Aged tumors exhibited significantly greater volume and a larger tumorigenic region when compared to young tumors, with single-cell RNA sequencing revealing enrichment of inflammatory and invasive genes.

Conclusions: Together, these findings identify LOX as a driver of tumor progression and a potential therapeutic target and demonstrate that the aged ECM alone is sufficient to promote breast cancer progression.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12915-026-02697-2.

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Cite

BibTeXRIS
BibTeX
@article{hawthorne2026transcriptomic,
  title = {{Transcriptomic insights into age-associated extracellular matrix promotion of breast cancer}},
  author = {Lauren Hawthorne and Gokhan Bahcecioglu and Jun Yang and Emilija Aleksandrovic and Erin Howe and Siyuan Zhang and Pinar Zorlutuna},
  journal = {BMC Biology},
  year = {2026},
  month = aug,
  doi = {10.1186/s12915-026-02697-2},
  url = {https://doi.org/10.1186/s12915-026-02697-2},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Transcriptomic insights into age-associated extracellular matrix promotion of breast cancer
AU  - Lauren Hawthorne
AU  - Gokhan Bahcecioglu
AU  - Jun Yang
AU  - Emilija Aleksandrovic
AU  - Erin Howe
AU  - Siyuan Zhang
AU  - Pinar Zorlutuna
PY  - 2026
DA  - 2026/08/08
JO  - BMC Biology
DO  - 10.1186/s12915-026-02697-2
UR  - https://doi.org/10.1186/s12915-026-02697-2
AB  - Background: Aging is a key risk factor for breast cancer; however, the independent effects of the aged extracellular matrix (ECM) remain understudied.  Results: To address this, we developed a novel hybrid in vivo model that enables the independent investigation of age-related ECM influences on breast cancer development and progression. To examine the effects of genes known to be enriched in a cancerous and aged microenvironment, we first seeded normal or stable knockdown cells onto decellularized ECM (dECM) from aged murine mammary glands and implanted them into young Rag1−/− mice. We identified LOX as a principal driver of tumor progression, with knockdown reducing invasion, in vitro and in vivo, and stress-related pathways. To further isolate the independent influence of ECM aging on tumor growth, normal MCF10A cells were seeded atop young or aged matrices and implanted. Aged tumors exhibited significantly greater volume and a larger tumorigenic region when compared to young tumors, with single-cell RNA sequencing revealing enrichment of inflammatory and invasive genes.  Conclusions: Together, these findings identify LOX as a driver of tumor progression and a potential therapeutic target and demonstrate that the aged ECM alone is sufficient to promote breast cancer progression.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12915-026-02697-2.
SN  - 1741-7007
ER  -