Comprehensive palmitoyl‐proteomic analysis identifies distinct protein signatures for large and small cancer‐derived extracellular vesicles

Mariscal, Javier; Vagner, Tatyana; Kim, Minhyung; Zhou, Bo; Chin, Andrew R.; Zandian, Mandana; Freeman, Michael R.; You, Sungyong; Zijlstra, Andries; Yang, Wei; Vizio, Dolores Di

doi:10.1080/20013078.2020.1764192

Cited by 47 publications

(44 citation statements)

References 68 publications

(127 reference statements)

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“…Recently STEAP1 was found to be expressed on PCa cell culture-derived EVs and, in-line with our work, abundance was not found to indicate disease aggressiveness [ 40 ]. It is however important to note that while we did not find prognostic significance from an evaluation of total STEAP1 EVs there may be sub-populations of STEAP1 EVs with predictive or prognostic capabilities.…”

Section: Discussionsupporting

confidence: 81%

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Khanna

Salmond

Lynn

et al. 2021

Prostate Cancer Prostatic Dis

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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, MSKCC, and SU2C/PCF Dream Team). Results Evaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. However, no association was found between total STEAP1 EV levels and disease recurrence or overall survival. Cohort data from prostate cancer tissue also found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified. Conclusions STEAP1 is known to be enriched on the cells of the prostate with potential clinical significance in prostate cancer. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer.

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Section: Discussionsupporting

confidence: 81%

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Khanna

Salmond

Lynn

et al. 2021

Prostate Cancer Prostatic Dis

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“…3 B). These differences would be related to those herein noticed with regards EVs size distribution, or as suggested by some reports, as consequence of differences in the membrane proteomic content of small and large EVs [ 47 ]. Moreover, EVs rupture due to UC high-speed centrifugations [ 46 ] or the reported variability on EVs yield depending on the equipment and operator technical variability could have affected the results [ 48 ].…”

Section: Discussionsupporting

confidence: 70%

Isolation and characterization of urine microvesicles from prostate cancer patients: different approaches, different visions

et al. 2021

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Background Because of their specific and biologically relevant cargo, urine extracellular vesicles (EVs) constitute a valuable source of potential non-invasive biomarkers that could support the clinical decision-making to improve the management of prostate cancer (PCa) patients. Different EV isolation methods differ in terms of complexity and yield, conditioning, as consequence, the analytical result. Methods The aim of this study was to compare three different isolation methods for urine EVs: ultracentrifugation (UC), size exclusion chromatography (SEC), and a commercial kit (Exolute® Urine Kit). Urine samples were collected from 6 PCa patients and 4 healthy donors. After filtered through 0.22 µm filters, urine was divided in 3 equal volumes to perform EVs isolation with each of the three approaches. Isolated EVs were characterized by spectrophotometric protein quantification, nanoparticle tracking analysis, transmission electron microscopy, AlphaScreen Technology, and whole miRNA Transcriptome. Results Our results showed that UC and SEC provided better results in terms of EVs yield and purity than Exolute®, non-significant differences were observed in terms of EV-size. Interestingly, luminescent AlphaScreen assay demonstrated a significant enrichment of CD9 and CD63 positive microvesicles in SEC and UC methods compared with Exolute®. This heterogeneity was also demonstrated in terms of miRNA content indicating that the best correlation was observed between UC and SEC. Conclusions Our study highlights the importance of standardizing the urine EV isolation methods to guaranty the analytical reproducibility necessary for their implementation in a clinical setting.

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“…Palmitoylation of Wnt-1, RASrelated protein Rab-7a, alpha-tubulin, and eIF3L initiation factor are some of the post-translational modifications mediated by FASN and regulated by AR that activate oncogenic signaling in PCa (23)(24)(25). More recently, a palmitoyl-protein signature has been described in PCa derived extracellular vesicles (EVs), membrane-enclosed particles that play an important role in cancer progression as source of nutrients, signaling molecules, immune modulators, and circulating biomarkers, uncovering a n o t h e r p o t e n t i a l m e c h a n i s m o f s u p p o r t t o P C a progression (26).…”

Section: Alterations In De Novo Fa Synthesismentioning

confidence: 99%

Prostate Cancer Progression: as a Matter of Fats

2021

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Advanced prostate cancer (PCa) represents the fifth cause of cancer death worldwide. Although survival has improved with second-generation androgen signaling and Parp inhibitors, the benefits are not long-lasting, and new therapeutic approaches are sorely needed. Lipids and their metabolism have recently reached the spotlight with accumulating evidence for their role as promoters of PCa development, progression, and metastasis. As a result, interest in targeting enzymes/transporters involved in lipid metabolism is rapidly growing. Moreover, the use of lipogenic signatures to predict prognosis and resistance to therapy has been recently explored with promising results. Despite the well-known association between obesity with PCa lethality, the underlying mechanistic role of diet/obesity-derived metabolites has only lately been unveiled. Furthermore, the role of lipids as energy source, building blocks, and signaling molecules in cancer cells has now been revisited and expanded in the context of the tumor microenvironment (TME), which is heavily influenced by the external environment and nutrient availability. Here, we describe how lipids, their enzymes, transporters, and modulators can promote PCa development and progression, and we emphasize the role of lipids in shaping TME. In a therapeutic perspective, we describe the ongoing efforts in targeting lipogenic hubs. Finally, we highlight studies supporting dietary modulation in the adjuvant setting with the purpose of achieving greater efficacy of the standard of care and of synthetic lethality. PCa progression is “a matter of fats”, and the more we understand about the role of lipids as key players in this process, the better we can develop approaches to counteract their tumor promoter activity while preserving their beneficial properties.

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Comprehensive palmitoyl‐proteomic analysis identifies distinct protein signatures for large and small cancer‐derived extracellular vesicles

Abstract: Vizio (2020) Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles,

Cited by 47 publications

References 68 publications

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Isolation and characterization of urine microvesicles from prostate cancer patients: different approaches, different visions

Prostate Cancer Progression: as a Matter of Fats

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