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Toll-Like Receptor-4 Signaling Pathway Influenced the Exosome Biogenesis and Angiogenesis in Human Triple-Negative
Parisa Khanicheragh1,2, Çığır Biray Avci3, Zahra Abbasi-Malati4
1Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Advanced Pharmaceutical Bulletin
|December 17, 2025
Summary
Toll-like receptor 4 (TLR4) signaling impacts breast cancer cell survival, angiogenesis, and exosome production. Inhibiting TLR4 may offer new therapeutic strategies for breast cancer.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Toll-like receptor (TLR) signaling is implicated in tumor cell biology.
- The role of TLR4 in breast cancer, specifically its effects on angiogenesis and exosome biogenesis, requires further elucidation.
Purpose of the Study:
- To investigate the impact of TLR4 signaling pathway stimulation and inhibition on angiogenesis and exosome (Exo) biogenesis in MDA-MB-231 breast cancer cells.
Main Methods:
- MDA-MB-231 cells were treated with lipopolysaccharide (LPS) to stimulate TLR4 and simvastatin (SIM) to inhibit it.
- Cell survival, TLR4 pathway gene expression, exosome properties, and angiogenesis markers were analyzed using MTT, real-time PCR, DLS, SEM, western blotting, and Transwell assays.
Main Results:
- Both LPS and SIM reduced cell survival in a dose-dependent manner.
- LPS upregulated TLR4 pathway genes (TLR4, NF-κB, IL-1β, MYD88, TRIF), while SIM downregulated them.
- LPS affected exosome diameter and markers (CD63, TSG101, Rab27), altered cell migration, and increased angiogenesis gene expression, whereas SIM reduced migration and angiogenesis markers.
Conclusions:
- The TLR4 signaling pathway modulates angiogenesis and exosome production in breast cancer cells.
- Targeting TLR4 presents a potential therapeutic avenue for breast cancer treatment.
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