Ancestry-linked stromal variations impact breast epithelial cell invasion

Area of Science:

• Oncology
• Cell Biology
• Genetics

Background:

• Breast cancer disproportionately affects women of African ancestry (AA) due to biological factors impacting disease outcome.
• A specific cell population expressing PROCR, ZEB1, and PDGFRα (PZP) is enriched in the breast stroma of healthy AA donors, and in tumor-adjacent tissues of European ancestry (EA) donors.

Purpose of the Study:

• To investigate the role of PZP cells in promoting epithelial cell invasion in breast cancer.
• To elucidate the molecular mechanisms by which PZP cells influence epithelial cell invasiveness.

Main Methods:

• Utilized 3D cell models to observe epithelial cell invasion.
• Analyzed leader-follower behaviors during extracellular matrix invasion.
• Investigated the involvement of AKT activation and fibronectin deposition.

Main Results:

• PZP cells conferred invasive capacity to epithelial cells from both AA and EA donors.
• Epithelial cell invasion was driven by AKT activation and fibronectin deposition from PZP cells.
• Blocking AKT activation significantly reduced epithelial cell invasiveness.

Conclusions:

• Intrinsic differences in normal breast tissues, such as PZP cell enrichment, are relevant to understanding breast cancer prognosis.
• PZP cells play a crucial role in promoting breast cancer cell invasion through specific molecular pathways.
• These findings contribute to understanding the molecular basis for worse breast cancer prognosis in certain patient cohorts.