Ancestry-linked stromal variations impact breast epithelial cell invasion
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View abstract on PubMed
Summary
This summary is machine-generated.Stromal cells expressing P ROCR, ZEB1, and PDGFRα (PZP cells) promote breast cancer invasion, regardless of genetic ancestry. Their enrichment in African ancestry breast tissue may contribute to disparities in outcomes.
Area Of Science
- Oncology
- Cell Biology
- Genetics
Background
- Breast cancer disproportionately affects women of African ancestry (AA), leading to higher mortality rates compared to European ancestry (EA) populations.
- Stromal cell populations, including those expressing P ROCR, ZEB1, and PDGFRα (PZP cells), are implicated in breast cancer progression.
- PZP cells are enriched in normal AA breast tissue and tumor-adjacent EA breast tissue, suggesting a role in ancestry-related disparities.
Purpose Of The Study
- To investigate the impact of PZP cells on the tumorigenic phenotypes of AA and EA human breast epithelial cells.
- To determine the contribution of PZP cells to the biological basis of breast cancer outcome disparities.
- To elucidate the mechanisms by which PZP cells influence breast cancer invasion.
Main Methods
- Utilized 3D cell models to simulate tumor invasion in vitro.
- Co-cultured human breast epithelial cells with PZP cells derived from different ancestries.
- Analyzed cellular behaviors, including extracellular matrix invasion and leader-follower dynamics.
- Investigated the roles of AKT signaling pathway activation and fibronectin deposition.
Main Results
- PZP cells conferred invasive capacity to breast epithelial cells independently of genetic ancestry.
- Observed leader-follower behaviors during extracellular matrix invasion mediated by PZP cells.
- Enhanced invasion resulted from a combination of AKT activation and fibronectin deposition by PZP cells.
- Blocking AKT activation significantly reduced the invasive capacity of epithelial cells.
Conclusions
- PZP cells play a crucial role in promoting breast cancer cell invasion through AKT activation and fibronectin deposition.
- The enrichment of PZP cells in AA breast tissue may contribute to the observed disparities in breast cancer prognosis.
- Understanding the role of PZP cells offers insights into the molecular basis of breast cancer outcome differences across ancestries.
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