Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells

Franzen, Carrie A.; Simms, Patricia; Huis, Adam F. Van; Foreman, Kimberly E.; Kuo, Paul C.; Gupta, Gopal N.

doi:10.1155/2014/619829

Cited by 180 publications

(172 citation statements)

References 28 publications

(25 reference statements)

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“…Nonetheless, flow imaging based assays, similar to conventional flow cytometric assays, are able to incorporate additional read outs such as staining for markers of immune activation and function thereby allowing direct associations to be made between TiO 2 interactions with single cells (adhesion or internalization) and the functional consequences of such interactions on the same cell. Like others, we found imaging cytometry a powerful technique for the analysis of particle localization, this was dependant on tailoring custom masks in order to obtain an accurate analysis 9, 10, 11, 12, 13, 14, 15. There is always potential for some particles analyzed to be attached externally to the front or back of the cells, the occurrence of false positive internalization events is random and at the same frequency within all data files as it is dependent only on the orientation of the cells as they are imaged.…”

Section: Discussionmentioning

confidence: 71%

Imaging flow cytometry assays for quantifying pigment grade titanium dioxide particle internalization and interactions with immune cells in whole blood

et al. 2017

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Pigment grade titanium dioxide is composed of sub‐micron sized particles, including a nanofraction, and is widely utilized in food, cosmetic, pharmaceutical, and biomedical industries. Oral exposure to pigment grade titanium dioxide results in at least some material entering the circulation in humans, although subsequent interactions with blood immune cells are unknown. Pigment grade titanium dioxide is employed for its strong light scattering properties, and this work exploited that attribute to determine whether single cell–particle associations could be determined in immune cells of human whole blood at “real life” concentrations. In vitro assays, initially using isolated peripheral blood mononuclear cells, identified titanium dioxide associated with the surface of, and within, immune cells by darkfield reflectance in imaging flow cytometry. This was confirmed at the population level by side scatter measurements using conventional flow cytometry. Next, it was demonstrated that imaging flow cytometry could quantify titanium dioxide particle‐bearing cells, within the immune cell populations of fresh whole blood, down to titanium dioxide levels of 10 parts per billion, which is in the range anticipated for human blood following titanium dioxide ingestion. Moreover, surface association and internal localization of titanium dioxide particles could be discriminated in the assays. Overall, results showed that in addition to the anticipated activity of blood monocytes internalizing titanium dioxide particles, neutrophil internalization and cell membrane adhesion also occurred, the latter for both phagocytic and nonphagocytic cell types. What happens in vivo and whether this contributes to activation of one or more of these different cells types in blood merits further attention. © 2017 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.

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Section: Discussionmentioning

confidence: 71%

Imaging flow cytometry assays for quantifying pigment grade titanium dioxide particle internalization and interactions with immune cells in whole blood

et al. 2017

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“…Exosomes derived from a bladder cancer cell line (SW780 cells) are internalized by cancer cells [30]. We have also shown that human breast cancer cells also internalize exosomes derived from human breast cancer lines and also from normal human mammary epithelial cells [4].…”

Section: Discussionmentioning

confidence: 62%

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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“…Heparin blocks the effect of MIBC exosomes on cell migration and invasion that uptake occurs through a heparin sulfate proteoglycan (HSPG)-dependent mechanism (76). HSPGs often act as a co-receptors for various integrin receptors and integrin receptors are wellestablished mediators of cell-matrix interactions (including tumor migration and invasion) (77,78,79,80,81).…”

Section: Hyaluronan Regulation and Glycosaminoglycanmentioning

confidence: 99%

Invasion Mechanisms of Bladder Cancer: A Molecular Review

Narter¹,

Sabuncu²

2016

jus

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ÖZBladder cancer (BC) is a very common cancer and it has high mortality rates, especially in late stages. BC is considered as a different disease in various stages and grades. Non-muscle-invasive BC and muscle-invasive BC have different properties. There are some prognostic factors for progression and recurrence rates of BC and we have some risk assessment methods. These factors are based on clinical findings and histopathological properties. We do not know which factors and molecular processes are effective in the invasion mechanism. In this review, we summarized possible invasion mechanisms of BC. KeywordsBladder cancer, invasion, metastasis, molecularMesane kanseri farklı evrelerde farklı birer hastalık gibi kabul ve tedavi edilir. Her evre tekrarlama ve ilerleme açısından farklı riskler taşır. Günümüzde bu tekrarlama ve ilerleme risklerini gösteren değişik hesaplama sistemleri tanımlansa da altta yatan moleküler, genetik ve çevresel faktörler net olarak gösterilememiştir. Mevcut risk hesaplama sistemleri klinik, makroskopik ve patolojik değerlendirme temellerine oturmaktadır. Derlemede özetlemeye çalıştığımız olası invazyon mekanizmaları aydınlatıldıkça prognostik yeni moleküler faktörlerin tanımlanması, hatta bu temelde yeni tedavi metodlarının geliştirilmesi mümkün olacaktır. Anahtar KelimelerMesane kanseri, invazyon, metastaz, moleküler IntroductionUrothelial tumors are classified as papillary and nonpapillary (solid) tumors. Histopathologically, more than 90% of bladder cancers (BCs) are urothelial (transitional) cell carcinomas (UCC or TCC). At the time of diagnosis, about 75% of BCs are non-muscle-invasive bladder cancer (NMIBC) and remaining 25% are muscle-invasive bladder cancer (MIBC). Phenotypes and genotypes of these cancers in various stages are different. In this context, 30% to 50% of NMIBCs recur after transurethral resection of the primary tumor, and 10% to 20% progress to MIBC. Many of high-grade carcinomas (including carcinoma in situ) invade the bladder wall and may metastasize to other sites. Additionally, nearly 50% of patients with MIBCs have occult distant metastases at the time of diagnosis (1,2). Recently, in the literature, there are many studies in which molecular, genetic and physical factors have been investigated in the progression and recurrence of the BC but it has not been fully outlined. All these factors affect the process of metastasis, invasion and resistance to therapy. Generally, major characteristics of malignant cancer cells are defined as self-sufficiency in growth signals, insensitivity to anti-growth signals, tissue invasion and metastasis, limitless replicative potential, sustained angiogenesis, and evading apoptosis. Additionally, tumor metastasis includes detachment, migration, invasion, intravasation, anoikis, evasion, and extravasation steps. In this review, we aimed to summarize the possible genetic, molecular and physical factors that are responsible for the progression and recurrence. Epithelial-Mesenchymal Transition and PlasticityMechanism of the...

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Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells

Cited by 180 publications

References 28 publications

Imaging flow cytometry assays for quantifying pigment grade titanium dioxide particle internalization and interactions with immune cells in whole blood

Imaging flow cytometry assays for quantifying pigment grade titanium dioxide particle internalization and interactions with immune cells in whole blood

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

Invasion Mechanisms of Bladder Cancer: A Molecular Review

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