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Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent

Author

Listed:
  • Brijesh Kumar

    (Indiana University School of Medicine
    Indian Institute of Technology (Banaras Hindu University))

  • Aditi S. Khatpe

    (Indiana University School of Medicine
    Indiana University School of Medicine)

  • Jiang Guanglong

    (Indiana University School of Medicine)

  • Katie Batic

    (Indiana University School of Medicine)

  • Poornima Bhat-Nakshatri

    (Indiana University School of Medicine)

  • Maggie M. Granatir

    (Indiana University School of Medicine)

  • Rebekah Joann Addison

    (Indiana University School of Medicine)

  • Megan Szymanski

    (Indiana University School of Medicine)

  • Lee Ann Baldridge

    (Indiana University School of Medicine)

  • Constance J. Temm

    (Indiana University School of Medicine)

  • George Sandusky

    (Indiana University School of Medicine)

  • Sandra K. Althouse

    (Indiana University School of Medicine)

  • Michele L. Cote

    (Richard M. Fairbanks School of Public Health, Indiana University)

  • Kathy D. Miller

    (Indiana University School of Medicine)

  • Anna Maria Storniolo

    (Indiana University School of Medicine)

  • Harikrishna Nakshatri

    (Indiana University School of Medicine
    Indiana University School of Medicine
    VA Roudebush Medical Center)

Abstract

The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.

Suggested Citation

  • Brijesh Kumar & Aditi S. Khatpe & Jiang Guanglong & Katie Batic & Poornima Bhat-Nakshatri & Maggie M. Granatir & Rebekah Joann Addison & Megan Szymanski & Lee Ann Baldridge & Constance J. Temm & Georg, 2023. "Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41473-6
    DOI: 10.1038/s41467-023-41473-6
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    References listed on IDEAS

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