Abstract
Abstract Multiple subtypes of prostate cancer can emerge in the advanced stages of disease, such as androgen receptor (AR+), AR indifferent with neuroendocrine features (AR-/NE+), and those without AR or NE features (double negative, DN). These latter variants are particularly aggressive and incredibly lethal. Extracellular vesicles (EVs), also known as exosomes, are small particles that are important mediators of cell-cell communication and have been nominated as potential biomarkers of disease state. We hypothesized that the proteome of extracellular vesicles contains enough information about their originating cell that they can distinguish between prostate cancer subtypes. To address this, we isolated EVs from prostate cancer cell lines of differing subtypes – AR+ (LNCaP, LNCaP95, C4-2, 22RV1), AR-/NE+(NCI-H660, EF1, LASCPC-01), and AR-/NE- (PC3, DU145) – and prepared the EV proteome for quantitative mass spectrometry analysis. This identified 2,000+ proteins in the EVs for each cell line. From our analysis, we found that the EVs from cell lines of similar subtypes clustered together with several hundred proteins statistically different between the three groups. Interestingly, we also found that EVs contained enough protein information to utilize already developed gene signature scores for AR or NE activity. EVs isolated from the AR-/NE+ cell line NCI-H660 scored over 90% with a 121 gene NE signature and included proteins such as SYP, CHGA, and UCHL1. EVs from all the AR+ cell lines displayed >80% AR activity that was driven by high expression of PSA and STEAP1. This supports the idea that we can use the proteome of tumor-derived EVs to identify signature molecular markers that are already known to the field to develop liquid-based biomarker assays. Further work in the clinical setting is needed to evaluate the ability for EVs to be specific, informative biomarkers for prostate cancer disease status. Citation Format: Megan Ludwig, Zoi Sychev, Abderrahman Day, Hannah Bergom, Justin Hwang, Justin M. Drake. Characterizing the landscape of extracellular vesicles from prostate cancer cell lines [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B047.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
