PO-193 The effect of chemotherapy induced intercellular communication on breast cancer metastasis

Introduction Breast cancer is amongst the most common types of cancer for women and the primary cause of cancer related death. The high mortality rates are due to the metastatic spread of cancer cells and tumour recurrence after therapy. Transferring their cargo from one cell to another, EVs (extracellular vesicles) are involved in maintaining homeostasis in normal physiology, but are deregulated in cancer. EVs have been shown to play particular roles in all hallmarks of cancer with great focus given on the various steps of the metastatic cascade. The aim of this project is to investigate the effect of chemotherapy induced intercellular communication via EVs on breast cancer metastasis. Material and methods Two chemotherapeutic agents commonly used in breast cancer therapy regimens, docetaxel and mitomycin C, were employed in this study. Metastatic potential after incubation with EVs derived from drug treated cells has been assessed by labelling with the glycosylation marker HPA (helix pomatia agglutinin), expression analysis of EMT (epithelial to mesenchymal transition) markers, motility and invasion assays. Results and discussions EVs from drug treated cells altered the glycosylation patterns of recipient cells as revealed by HPA labelling, while EVs from non-treated cells showed no effect. EVs from docetaxel treated cells enhanced invasiveness and motility of recipient cells and lowered the expression of the epithelial marker CDH1. Conclusion These results suggest that cells that have survived chemotherapy release EVs that are able to enhance the metastatic capacity of intact cells.