The effect of stressed cell-derived exosomes on metastatic activity of ovarian and breast cancer cell lines in vitro
Metastasis is one of the main causes of cancer related death worldwide; hence elucidation of this mechanism, at least in part, will support development of effective therapies to improve the morbidity and mortality of people with cancer. Cells continually expel a large number and variety of extracellular vesicles. Of these secreted vesicles, exosomes have been studied extensively over the past decade. Exosomes are between 30–100 nm in diameter and contain protein and nucleic acids. They have only very recently become appreciated as communication mediators that transport signals between cells. It was hypothesised that exosomes secreted by more metastatic cells may have the ability to increase the motility of less metastatic cells, and vice versa. The motile capacity of nine ovarian cancer cell lines was established using the scratch wound healing assay. Following this, exosome swapping experiments were performed between more and less metastatic cells. It was shown that exosomes were unable to influence the motility of recipient cells, irrespective of the metastatic phenotype of their cells of origin. It was also hypothesised that exosomes derived from stressed cells increase the invasive capacity of recipient cells. Exosomes were extracted from heat shocked or cisplatin treated cells and were introduced to naïve cells. The invasive capacity of recipient cells was tested following administration of stressed cellderived exosomes. It was discovered that cell invasiveness increased following uptake of either heat shock or cisplatin exosomes. Additionally, both heat shock and cisplatin exosomes were found to be statistically significantly smaller in diameter than those extracted from control cells, when measured using transmission electron microscopy. This has implications for patients with cancer because tumour cells that resist, but become stressed during administration of cisplatin therapy, could be expelling exosomes that increase the invasiveness of neighbouring cancer cells, and the cells of the surrounding healthy stroma.
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