Introduction: Tumor-nerve interactions play a critical role in cancer progression, invasion, and metastasis. However, how tumor aggressiveness and hypoxic conditions influence neuronal remodeling remains incompletely understood in breast cancer.
Methods: This study investigated the effects of highly metastatic 4T1 and less aggressive EMT6 breast cancer cells, as well as their conditioned media, on dorsal root ganglion (DRG) axon elongation under normoxic and hypoxic conditions. Eight experimental groups were analyzed. Axon lengths were quantified using NeuronJ software in triplicate experiments. Statistical analyses were performed using one-way ANOVA followed by Tukey’s post-hoc test.
Results: Under normoxic conditions, 4T1 cells induced the most pronounced axon elongation compared to EMT6 cells and control groups. In contrast, hypoxia consistently suppressed neurite extension across all experimental conditions. Additionally, conditioned media alone exerted weaker effects than direct co-culture systems, indicating the importance of juxtacrine signaling and direct cell-to-cell interactions in tumor-neuron communication.
Conclusion: These findings demonstrate that tumor aggressiveness and oxygen availability differentially regulate neuronal remodeling in breast cancer. The results highlight neuron-tumor crosstalk as a potential therapeutic target in breast cancer progression.
Keywords: Axon elongation, breast cancer, dorsal root ganglia (DRG),