Investigation of Conditioned Media-Mediated Communication between Pancreatic Cancer Cells and Neurons

Objective: Pancreatic cancer (PCa) is one of the deadliest cancers, characterized by prominent pathological changes in nerves. PCa cells invade nerves, termed neural invasion, driven by bidirectional interactions between cancer cells and nerves, leading to severe pain and shorter patient survival. However, the understanding of this communication remains limited, particularly in cell culture experiments. Therefore, we investigated the effect of soluble factors derived from neurons and PCa cells on behaviors of each cell type. Material and Methods: SH-SY5Y cells were differentiated into neurons, and the differentiation efficacy was confirmed by immunofluorescence staining and Western blot. PANC-1 and BxPC-3 PCa cells were exposed to conditioned media (CM) from neurons, and changes in migration and invasion were evaluated by wound healing and transwell invasion assay, respectively. Similarly, neurons were treated with CM derived from PANC-1 or BxPC-3 cells, and changes in migration and neuronal markers were assessed. Results: Neuron-derived CM showed no significant impact on PCa cell migration and invasion. Similarly, exposure of neurons from PCa cells did not significantly migration of them, but slightly increased neurite formation. Conclusion: This study provided preliminary information on the possible effect of CM on the interaction between PCa cells and neurons. However, the absence of other cell types in the TME (such as fibroblasts and Schwann cells) in the study design might be a reason for not obtaining the expected changes. Therefore, different culture models and further research are needed to investigate the role of cells and factors that may potentially contribute to cancer-neuron interaction.