Bladder Cancer Exosomes Contain EDIL-3/Del1 and Facilitate Cancer Progression

Beckham, Carla; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K.; Scosyrev, Emelian; Messing, Edward M.; Lee, Yi-Fen

doi:10.1016/j.juro.2014.02.035

Cited by 167 publications

(160 citation statements)

References 28 publications

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“…Choi and colleagues [7] demonstrated that a decrease in Del-1 mRNA in lung cancer cells was correlated with p53 activity, and treatment with an adenovirus expressing Del-1 promoted the proliferation of lung adenocarcinoma cells without altering the expression of apoptosis-regulating molecules such as BAX, PUMA, and Bcl-2. Second, Del-1 may be a novel regulator of epithelial-mesenchymal transition via ERK and TGF-β signaling and may ultimately promote tumor migration, invasion, and metastasis in HCC, bladder, and breast cancer [9,19,20]. Del-1 also plays an important role in angiogenesis by enhancing the recruitment of endothelial cells and capillary tube formation, thereby aiding cancer cell metastasis.…”

Section: Discussionmentioning

confidence: 99%

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer

Lee

Kim

et al. 2018

Oncology

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Objective: A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Methods: Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. Results: While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. Conclusion: While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer

Lee

Kim

et al. 2018

Oncology

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“…Thus there is a feedback mechanism regulating the release of exosomes [4]. Exosomes also promote the migration of urothelial cells and angiogenesis [15]. Proliferation of bladder tumor cells is promoted by exosomes and apoptosis is inhibited [31].…”

Section: Discussionmentioning

confidence: 99%

“…Beckham et al [15] have demonstrated that bladder cancer derived exosomes from both cell lines and urine of patients promote angiogenesis and bladder cancer migration. They also showed that bladder cancer derived exosomes contained high concentrations of EDIL-3 relative to exosomes derived from healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Human urinary exosomes in bladder cancer patients: properties, concentrations and possible clinical application

Riches

Powis

Mullen

et al. 2016

Bladder

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OBJECTIVE:High grade bladder cancer is extremely aggressive. Early detection is thus an important challenge. Development of non-invasive diagnostic tools particularly using urine samples could be of importance in the diagnosis and surveillance of these patients. Exosomes are small vesicles present in the urine and have the potential to be used as biomarkers of cancer. Thus studies of the properties and concentrations of these particles in bladder cancer patients are of importance. MATERIALS AND METHODS:The concentration of exosomes present in urine was determined by nanoparticle tracking analysis using a Nanosight LM10 unit. Clinical urine samples were routinely collected and fixed using Preservcyt. The morphology of exosomes was studied in electron micrographs and characteristic exosome markers using Western blots. RESULTS:The exosome concentration of fixed samples stored at room temperature was constant for 48 hours and the same as fresh samples. Exosomes derived from patients presenting for a transurethral resection of their bladder tumor exhibited the exosome markers ALIX and TSG101 and also the classic cup shaped appearance in electron micrographs. The concentration of exosomes in patients presenting for transurethral resection of a bladder tumor was significantly greater than in patients presenting for check cystoscopy with no recurrence (median 77.2 × 10 8 per ml compared with 38.8 × 10 8 per ml, P < 0.001). A ROC analysis (area under the curve 77.4%) suggested that a suitable cut-off concentration of 85 × 10 8 per ml is associated with a sensitivity of 43% and specificity of 91% for diagnosing bladder cancer. CONCLUSIONS:Thus the concentration and properties of exosomes can be conveniently studied in fixed urine samples derived from bladder cancer patients. The characteristic properties of exosomes were preserved and increased numbers were found in patients presenting for transurethral resection of their tumor. With an appropriate cut-off value, urinary exosome concentrations may have utility in excluding a cancer recurrence when monitoring patients successfully treated for bladder cancer.

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“…From 24 proteins known to be differentially expressed in bladder cancer patients, one (TACSTD2) was found to also be present at significantly elevated levels in EVs isolated from urine [107]. EDIL-3, another protein found to play a role in cell migration and tube formation and was present at elevated levels in bladder cancer patients [108]. Association of EDIL-3 expression in tumor tissues with EDIL-3 levels in urine exosomes posits urinary EVs as a source of biomarkers for bladder cancer detection.…”

Section: Extracellular Vesicles (Ev) Isolationmentioning

confidence: 99%

Microdevices for Non-Invasive Detection of Bladder Cancer

et al. 2017

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Bladder cancer holds the record for the highest lifetime cost on a per-patient basis. This is due to high recurrence rates, which necessitate invasive and costly long-term evaluation methods such as cystoscopy and imaging. Microfluidics is emerging as an important approach to contribute to initial diagnosis and follow-up, by enabling the precise manipulation of biological samples. Specifically, microdevices have been used for the isolation of cells or genetic material from blood samples, sparking significant interest as a versatile platform for non-invasive bladder cancer detection with voided urine. In this review, we revisit the methods of bladder cancer detection and describe various types of markers currently used for evaluation. We detail cutting-edge technologies and evaluate their merits in the detection, screening, and diagnosis of bladder cancer. Advantages of microscale devices over standard methods of detection, as well as their limitations, are provided. We conclude with a discussion of criteria for guiding microdevice development that could deepen our understanding of prognoses at the level of individual patients and the underlying biology of bladder cancer development. Collectively, the development and widespread application of improved microfluidic devices for bladder cancer could drive treatment breakthroughs and establish widespread, tangible outcomes on patients' long-term survival.

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Bladder Cancer Exosomes Contain EDIL-3/Del1 and Facilitate Cancer Progression

Abstract: Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies.

Cited by 167 publications

References 28 publications

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer

Human urinary exosomes in bladder cancer patients: properties, concentrations and possible clinical application

Microdevices for Non-Invasive Detection of Bladder Cancer

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