Characterisation of the membrane composition and function of extracellular vesicles from prostate cancer cells

In prostate cancer, and other solid malignancies, the tetraspanins CD9 and CD151 are involved in the progression and advancement to metastasis. As the tumour progresses, the abundance of CD9 and CD151 are typically altered, with CD9 becoming downregulated and CD151 becoming upregulated. Tetraspanins are also recovered on the membranes of extracellular vesicles (EVs), including exosomes and microvesicles, that are secreted or bud from most cells of the body into the extracellular space. EVs are important intercellular communicators and transport a cargo of nucleic acids, proteins and lipids to target cells at local and distant sites in the body. EVs are recovered from most biological fluids, including blood and urine, and as such, their use as diagnostic and prognostic markers of disease is gaining interest. One key aspect of EV composition that has been largely overlooked to date is their lipidome. The overall aim of this project was to characterise the lipidome of EVs derived from non-tumourigenic, tumourigenic and metastatic prostate cell lines. However, as tetraspanins interact with lipids and lipid rafts, an assessment of the lipidome of EVs from prostate cell lines with modified CD9 and CD151 abundance was also performed, and the effects of these EVs on thrombin formation was determined. Further, the effects of altered cell culture media conditions on the lipidome of cells was assessed.