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

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, duri...

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Autores principales: Hosseini-Beheshti, Elham, Choi, Wendy, Weiswald, Louis-Bastien, Kharmate, Geetanjali, Ghaffari, Mazyar, Roshan-Moniri, Mani, Hassona, Mohamed D., Chan, Leslie, Chin, Mei Yieng, Tai, Isabella T., Rennie, Paul S., Fazli, Ladan, Guns, Emma S. Tomlinson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924741/
https://www.ncbi.nlm.nih.gov/pubmed/26840259
http://dx.doi.org/10.18632/oncotarget.7052
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author Hosseini-Beheshti, Elham
Choi, Wendy
Weiswald, Louis-Bastien
Kharmate, Geetanjali
Ghaffari, Mazyar
Roshan-Moniri, Mani
Hassona, Mohamed D.
Chan, Leslie
Chin, Mei Yieng
Tai, Isabella T.
Rennie, Paul S.
Fazli, Ladan
Guns, Emma S. Tomlinson
author_facet Hosseini-Beheshti, Elham
Choi, Wendy
Weiswald, Louis-Bastien
Kharmate, Geetanjali
Ghaffari, Mazyar
Roshan-Moniri, Mani
Hassona, Mohamed D.
Chan, Leslie
Chin, Mei Yieng
Tai, Isabella T.
Rennie, Paul S.
Fazli, Ladan
Guns, Emma S. Tomlinson
author_sort Hosseini-Beheshti, Elham
collection PubMed
description Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized 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, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression.
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spelling pubmed-49247412016-07-13 Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment Hosseini-Beheshti, Elham Choi, Wendy Weiswald, Louis-Bastien Kharmate, Geetanjali Ghaffari, Mazyar Roshan-Moniri, Mani Hassona, Mohamed D. Chan, Leslie Chin, Mei Yieng Tai, Isabella T. Rennie, Paul S. Fazli, Ladan Guns, Emma S. Tomlinson Oncotarget Research Paper Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized 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, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression. Impact Journals LLC 2016-01-28 /pmc/articles/PMC4924741/ /pubmed/26840259 http://dx.doi.org/10.18632/oncotarget.7052 Text en Copyright: © 2016 Hosseini-Beheshti et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Hosseini-Beheshti, Elham
Choi, Wendy
Weiswald, Louis-Bastien
Kharmate, Geetanjali
Ghaffari, Mazyar
Roshan-Moniri, Mani
Hassona, Mohamed D.
Chan, Leslie
Chin, Mei Yieng
Tai, Isabella T.
Rennie, Paul S.
Fazli, Ladan
Guns, Emma S. Tomlinson
Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
title Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
title_full Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
title_fullStr Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
title_full_unstemmed Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
title_short Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
title_sort exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924741/
https://www.ncbi.nlm.nih.gov/pubmed/26840259
http://dx.doi.org/10.18632/oncotarget.7052
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