Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment

Prostate cancer (PCa) is the leading type of cancer diagnosed in men. Studies on tumour-related extracellular vesicles (EVs) suggest that exosomes play a significant role in paracrine signaling pathways thus potentially influencing cancer progression via different mechanisms.

During last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. We have previously described the role of exosomes as potential biomarkers for PCa. Differences in proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirmed that exosomes are good candidates for future biomarker studies. Our extensive proteomic analysis completed alongside with the evidence of exosome uptake into a local tumour microenvironment have encouraged us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. In this study, we hypothesize that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis in LNCaP and RWPE-1 cells increase cancer cell proliferation and induce cell migration. Consistently with our in vitro findings, we have demonstrated that exosomes increase tumor volume and PSA level in vivo when xenograft bearing mice were administered intravenously with DU145 exosomes. This research suggests that exosomes derived from PCa cells, regardless of the androgen receptor phenotype, attribute positively the of mechanisms that contribute to PCa progression.

Oncotarget. 2016 Jan 28 [Epub ahead of print]

Elham Hosseini-Beheshti, Wendy Choi, Louis-Bastien Weiswald, Geetanjali Kharmate, Mazyar Ghaffari, Mani Roshan-Moniri, Mohamed D Hassona, Leslie Chan, Mei Yieng Chin, Isabella T Tai, Paul S Rennie, Ladan Fazli, Emma S Tomlinson Guns

Department of Experimental Medicine University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , The Vancouver Prostate Centre University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , The Vancouver Prostate Centre University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Department of Experimental Medicine University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Department of Experimental Medicine University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , The Vancouver Prostate Centre University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , The Vancouver Prostate Centre University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , The Vancouver Prostate Centre University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Department of Urologic Sciences University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Department of Urologic Sciences University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada. , Department of Urologic Sciences University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada.

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