Modulation of paracrine signaling by CD9 positive small extracellular vesicles mediates cellular growth of androgen deprived prostate cancer (original) (raw)
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Emerging Role of Extracellular Vesicles in Prostate Cancer
Endocrinology
Prostate cancer (PCa) is the second most common cancer among men in the United States. While the use of prostate-specific antigen has improved the ability to screen and ultimately diagnose PCa, there still remain false positives due to noncancerous conditions in the prostate gland itself and other prognostic biomarkers for PCa are needed. Contents within extracellular vesicles (EVs) have emerged as promising biomarkers that can give valuable information about disease state, and have the additional benefit of being acquired through noninvasive liquid biopsies. Meaningful communication between cancer cells and the microenvironment are carried by EVs, which impact important cellular processes in prostate cancer such as metastasis, immune regulation, and drug resistance.
Proteomics, 2017
Current treatments for advanced prostate cancer focus on inhibition of the androgen receptor (AR) by androgen deprivation therapy (ADT). However, complex interactions mediated by tumour suppressors, oncogenes, aberrations of AR expression, or de novo androgen production have been shown to induce the adaptive response of prostate cancer, leading to the development of castration resistant prostate cancer (CRPC). In this study, we report the effects of AR antagonist, enzalutamide on the protein contents of extracellular vesicles (EVs). EVs mediate cell-to-cell communication and increasing evidence shows the role of EVs in promoting cancer survival and metastasis. We found that treatment with enzalutamide alters the secretion of EVs, one of which is a plasma membrane calcium pump, ATP2B1/PMCA ATPase, as an AR-regulated EV protein. We highlight the networks of interactions between AR, Ca2+ and ATP2B1, where the extracellular proteins thrombospondin-1, gelsolin and integrinß1 were previou...
Molecular carcinogenesis, 2017
There is increasing evidence that cancer dissemination and metastasis establishment may not only be due to the movement of tumor cells. Content of extracellular vesicles (EVs) secreted by tumor cells may also reflect the origin of these cells. Some molecules that constitute these EVs have already been used as targets for detection of specific tumors. However, to the best of our knowledge, EVs from biopsies and plasma have not yet been compared nor thoroughly investigated as triggers of malignant transformation and metastatic niche formation. To evaluate the role of EVs in the cellular microenvironment, we have treated the normal epithelial prostate cell lines, RWPE-1 and PNT-2, with a pool of EVs from biopsies of prostate primary tumors (bEVs), biopsies of benign prostate hyperplasia (hEVs), plasma of prostate cancer (PCa) patients (pEVs) or plasma of healthy individuals (pnEVs). Each of the four pools consisted of isolated EVs from several subjects, of which PCa patients were in di...
Oncotarget, 2016
Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa.
Cell Death & Disease
Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-β5, Survivin, TGF-β, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follo...
Journal of extracellular vesicles, 2018
Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography-mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundan...
Clinical significance of STEAP1 extracellular vesicles in prostate cancer
2021
Background Extracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance. Methods STEAP1 was identified on EVs in prostate cancer patient plasma. EVs were validated using electron microscopy, Western blot, nanoparticle tracking analysis, and nanoscale flow cytometry. STEAP1-positive EVs were quantified for 121 males with prostate cancer and 55 healthy age-matched control males. An evaluation of STEAP1 in prostate cancer tissue was also performed using established prostate cancer cohort data (TCGA, MSK...