The role of extracellular vesicles (EVs) as vehicles for cell-to-cell communication between a tumour and its environment is a relatively new concept. The hypothesis that EVs may be critical in co-opting tissues by tumours to generate distant metastatic niches is particularly pertinent to prostate cancer (PCa), where metastatic-tropism to bone predominates over other tissue types. The potential role of EVs as a means of communication between PCa cells and cells of the bone stroma such as osteoblasts, is yet to be fully explored. In this study, we demonstrate that PCa cell EVs both enhance osteoblast viability and produce a significantly more supportive growth environment for PCa cells when grown in co-culture with EV-treated osteoblasts (p < 0.005). Characterisation of the RNA cargo of EVs produced by the bone-metastatic PCa cell line PC3, highlights the EV-RNA cargo is significantly enriched in genes relating to cell surface signalling, cell-cell interaction, and protein translation (p < 0.01). Using novel techniques to track RNA, we demonstrate the delivery of a set of PCa-RNAs to osteoblast via PCa-EVs and show the effect on osteoblast endogenous transcript abundance. Taken together, by using proof-of-concept studies we demonstrate for the first time the contribution of the RNA element of the PCa EV cargo, providing evidence to support PCa EV communication via RNA molecules as a potential novel route to mediate bone metastasis. We propose targeting PCa EVs could offer a potentially important preventative therapy for men at risk of metastatic PCa.
Oncogene. 2018 Oct 23 [Epub ahead of print]
C Probert, T Dottorini, A Speakman, S Hunt, T Nafee, A Fazeli, S Wood, J E Brown, V James
School of Veterinary Medicine and Science, University of Nottingham, Nottingham, LE12 5RD, UK., School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA, UK., Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Jessop Wing, Tree Root Walk, Sheffield, S10 2SF, UK., Department of Oncology and Metabolism, Western Park Hospital, University of Sheffield, Whitham Road, Sheffield, S10 2SJ, UK., School of Veterinary Medicine and Science, University of Nottingham, Nottingham, LE12 5RD, UK. .