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Beitragstitel Monitoring altered PSMA expression in prostate cancer-derived extracellular vesicles via Advanced Image Flow Cytometry (ISX)
Beitragscode P061
Autor:innen
  1. Lukas Prause Universitätsspital Zürich Präsentierende:r
  2. Christopher Millan Universitätsspital Zürich
  3. Natalie Hensky Universitätsspital Zürich
  4. Cedric Poyet University Hospital Zurich and University of Zurich
  5. Thomas Hermanns Universitätsspital Zürich
  6. Daniel Eberli Universitätsspital Zürich
Präsentationsform moderierte Poster
Themengebiete
  • Grundlageforschung
Abstract-Text New diagnostic and therapeutic options for patients with prostate cancer are urgently needed. Prostate-specific membrane antigen (PSMA)-based imaging and therapy are increasingly used for prostate cancer management. Unfortunately, as a membrane protein, PSMA is not found as a soluble protein in the blood and therefore has limited utility as a diagnostic biomarker. However, PSMA has reportedly been observed as a cargo protein of prostate cancer-derived extracellular vesicles (EVs). EVs are small membrane vesicles released by all cells that transport functional biomolecules (protein, DNA, RNA) of a parent cell. The EVs are delivered not only to the local microenvironment but also act systemically by entering the circulation and promote many aspects of cancer spreading including angiogenesis, invasion and proliferation and contribute to cancer cell plasticity by regulating epithelial to mesenchymal transition (EMT).
We demonstrate altered PSMA expression on EVs derived from prostate cancer cell cultures (C4-2, LNCaP) in response to novel next-generation androgen receptor inhibitor (enzalutamide), a standard chemotherapy agent (docetaxel), a novel experimental nonsteroidal antiandrogen (Epi-001) that binds covalently to the N-terminal domain of the androgen receptor and dihydrotestosterone (DHT). Transmission electron microscopy, nanoparticle tracking analysis and simple Western (WES) analysis show stable size distribution and amount of EVs produced by treated and non-treated cells. Using advanced image-based flow cytometry, altered CD9/PSMA expression could be detected in EVs isolated from cell culture supernatants of LNCaP and C4-2 prostate cancer cells following their treatment.

Additionally, EVs were isolated from the plasma of prostate cancer patients who participated in the proCOC biobank campaign at the USZ. Plasma was taken and stored from patients both pre- and post- prostatectomy. Measuring EV-PSMA expression in patient plasma revealed a striking decrease in patient blood following surgical intervention.

Measuring PSMA expression on extracellular vesicles might pave the way to use image flow cytometry of EVs to develop a blood based diagnostic test for prostate cancer patients with a wide range of possible applications including: 1) monitoring response to therapy and, 2) early indications of potential relapse.