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Hypoxia-Driven Extracellular Vesicles Promote Pro-Metastatic Signalling in LNCaP Cells via Wnt and EMT Pathways
Melissa Santos1, Khansa Bukhari1, Irem Peker-Eyüboğlu1,2
1Cancer Mechanisms and Biomarkers Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK.
Biology
|September 27, 2025
Summary
Hypoxia-driven extracellular vesicles (EVs) from prostate cancer cells promote cancer spread and aggressiveness by reprogramming normal and less aggressive prostate cells via Wnt signalling and epithelial-mesenchymal transition (EMT).
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Tumor microenvironment, particularly hypoxia, drives prostate cancer (PCa) aggressiveness and therapy resistance.
- Hypoxia-induced extracellular vesicles (EVs) can transfer bioactive molecules, altering recipient cell behavior.
- Prostate cancer progression involves changes in cell signaling pathways like Wnt and epithelial-mesenchymal transition (EMT).
Purpose of the Study:
- To investigate if EVs from hypoxia-conditioned prostate cancer cells enhance malignant traits in other prostate cell lines.
- To determine the role of Wnt signaling and EMT in hypoxia-derived EV-mediated reprogramming.
- To assess the impact of these EVs on cell motility, invasiveness, and gene expression.
Main Methods:
- PC3 prostate cancer cells were cultured under hypoxic (1% O2) or normoxic conditions.
- Extracellular vesicles (EVs) were isolated from these conditioned cells.
- EVs were applied to LNCaP (low metastatic potential) and PNT2 (non-tumorigenic) prostate cell lines for analysis.
- Gene expression (HIF-1α, Vimentin, N-cadherin, Wnt3A, Wnt5A, Fzd7, E-cadherin) and functional assays (motility, invasiveness) were performed.
Main Results:
- Hypoxia-derived EVs increased HIF-1α expression and upregulated mesenchymal markers (Vimentin, N-cadherin) and Wnt-related genes (Wnt3A, Wnt5A, Fzd7).
- These EVs suppressed the epithelial marker E-cadherin.
- LNCaP cells treated with hypoxia-derived EVs showed increased motility and invasiveness.
- PNT2 cells exhibited transcriptomic reprogramming after exposure to hypoxia-derived EVs.
Conclusions:
- Hypoxia-driven EVs from metastatic prostate cancer cells can propagate pro-metastatic signaling.
- These EVs reprogram less aggressive and normal prostate cells, potentially driving tumor progression.
- Extracellular vesicles represent a promising therapeutic target for managing prostate cancer progression.
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