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Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model
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Ancestry-linked stromal variations impact breast epithelial cell invasion.

Madison G Schmidtmann1, Victoria Elliott1, James W Clancy1

  • 1Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.

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Summary

Breast cancer prognosis may be influenced by specific cell populations (PZP cells) found in breast tissue. These cells promote invasive behavior in epithelial cells, contributing to understanding disparities in African ancestry women.

Keywords:
CancerGenomicsHuman Genetics

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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.