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Prostasomes as a source of diagnostic biomarkers for prostate cancer
Carla Zijlstra, Willem Stoorvogel
Carla Zijlstra, Willem Stoorvogel
Published April 1, 2016
Citation Information: J Clin Invest. 2016;126(4):1144-1151. https://doi.org/10.1172/JCI81128.
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Review Series

Prostasomes as a source of diagnostic biomarkers for prostate cancer

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Abstract

New biomarkers are needed to improve the diagnosis of prostate cancer. Similarly to healthy cells, prostate epithelial cancer cells produce extracellular vesicles (prostasomes) that can be isolated from seminal fluid, urine, and blood. Prostasomes contain ubiquitously expressed and prostate-specific membrane and cytosolic proteins, as well as RNA. Both quantitative and qualitative changes in protein, mRNA, long noncoding RNA, and microRNA composition of extracellular vesicles isolated from prostate cancer patients have been reported. In general, however, the identified extracellular vesicle–associated single-marker molecules or combinations of marker molecules require confirmation in large cohorts of patients to validate their specificity and sensitivity as prostate cancer markers. Complications include variable factors such as prostate manipulation and urine flux, as well as masking by ubiquitously expressed free molecules and extracellular vesicles from tissues other than the prostate. Herein, we propose that the most promising methods include comprehensive combinational screening for (mutant) RNA in prostasomes that are immunoisolated with antibodies targeting prostate-specific epitopes.

Authors

Carla Zijlstra, Willem Stoorvogel

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Figure 1

Morphologic changes and prostasome release during PCa progression.

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Morphologic changes and prostasome release during PCa progression.
(A) N...
(A) Normal prostate epithelium with secretory luminal cells and basal cells, which are found between the luminal cells and the underlying basal lamina (neuroendocrine cells are not shown). Epithelial cells release prostasomes into the prostatic duct. Prostasomes can be formed by inward budding of MVE and are then secreted as exosomes by fusion of the MVE delimiting membrane with the plasma membrane. Alternatively, prostasomes may represent microvesicles (MV), which are formed by outward budding and pinching directly from the plasma membrane. (B) Intraepithelial neoplasia is characterized by loss of basal cells, neoplasia of luminal cells, and an intact basal lamina. (C) Metastasis, characterized by loss of the basal lamina, loss of polarity of luminal cells, and release of prostasomes into the underlying tissue and blood. The release of apoptotic bodies and intact cells is not shown.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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