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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.

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    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.

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    A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion

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    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.