Radiotherapeutic treatment of prostate cancer cells promotes the release of potentially deleterious and immunologically active extracellular vesicles

You have accessJournal of UrologyCME1 Apr 2023PD04-12 RADIOTHERAPEUTIC TREATMENT OF PROSTATE CANCER CELLS PROMOTES THE RELEASE OF POTENTIALLY DELETERIOUS AND IMMUNOLOGICALLY ACTIVE EXTRACELLULAR VESICLES Ryan Molony, Sarah Kerns, Brian Marples, Emmanuel Oshodi, YuhChyau Chen, and Yi-Fen Lee Ryan MolonyRyan Molony More articles by this author , Sarah KernsSarah Kerns More articles by this author , Brian MarplesBrian Marples More articles by this author , Emmanuel OshodiEmmanuel Oshodi More articles by this author , YuhChyau ChenYuhChyau Chen More articles by this author , and Yi-Fen LeeYi-Fen Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003228.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: One in four prostate cancer (PCa) patients will develop late hematuria and other delayed bladder toxicities following radiotherapy (RT) through poorly understood mechanisms. Membrane-enclosed extracellular vesicles (EVs) are released from tumor and non-tumor cells at baseline, and their composition can change markedly in response to stimuli. The impact of RT-induced EV (RT-EV) release from PCa cells or other cell populations in the tumor microenvironment, including immune cells, have yet to be characterized. Here, we examined the dynamics and composition of RT-EVs released by PCa cells and immune cells in response to irradiation, and their association with bladder tissue toxicity. METHODS: Urinary EV cargo proteins in pre- and post-RT PCa patient samples were analyzed and compared by LC-MS/MS. The impact of RT on EV release kinetics was analyzed by nanoparticle tracking analysis. RT-EVs and naïve EVs were collected from PCa patients and PCa cells lines (C4-2 and LNCaP). Their mechanistic effects on normal SV-HUC urothelial cells were assessed, including cellular viability, reactive oxygen species (ROS) production, and cytokine release. The effects of RT-EVs and RT on the activation of immune cell populations were monitored by treating Jurkat T cells or HL-60-derived neutrophils with RT-EVs or irradiating these cells and evaluating activation, cytokine release, and ROS production. RESULTS: The post-RT urinary EVs of a PCa patient who later developed hematuria were enriched for potentially caustic neutrophil-associated proteins relative to EVs from a hematuria-free patient. RT significantly enhanced the release of EVs from PCa cell lines and neutrophils, and these RT-EVs or direct irradiation promoted increased ROS production by HL-60 neutrophils, Jurkat T cells, and SV-HUC urothelial cells while also increasing interleukin (IL)-1β release from SV-HUC cells consistent with the induction of a damage-associated innate immune response. CONCLUSIONS: These results suggest RT can provoke the release of immunologically active and potentially deleterious EVs from PCa cells and local immune cell populations that can contribute to oxidative stress and inflammatory response induction in local and distant cell populations including neutrophils, T cells, and urothelial cells, potentially driving a feedback loop exacerbating RT-associated tissue damage. Source of Funding: University of Rochester Medical Center Departmental Funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e146 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryan Molony More articles by this author Sarah Kerns More articles by this author Brian Marples More articles by this author Emmanuel Oshodi More articles by this author YuhChyau Chen More articles by this author Yi-Fen Lee More articles by this author Expand All Advertisement PDF downloadLoading ...