Sialyl-Tn identifies muscle-invasive bladder cancer basal and luminal subtypes facing decreased survival, being expressed by circulating tumor cells and metastases

Lima, Luís; Neves, Manuel; Oliveira, Marta I.; Diéguez, Lorena; Freitas, Rui; Azevedo, Rita; Gaiteiro, Cristiana; Soares, Janine; Ferreira, Dylan; Peixoto, Andreia; Fernandes, Elisabete; Montezuma, Diana; Tavares, Ana; Ribeiro, Ricardo; Castro, Ana; Oliveira, Manuel Castanheira de; Fraga, Avelino; Reis, Celso A.; Santos, Lúcio Lara; Ferreira, José Alexandre

doi:10.1016/j.urolonc.2017.08.012

Cited by 39 publications

(44 citation statements)

References 13 publications

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“…STn labeling was found to be specific as confirmed by the loss of signal upon sample treatment with neuraminidase ( Figure S2B). Moreover, STn expression in corresponding tissue sections was evaluated and found to be lower in low-grade NMIBC in comparison to high-grade lesions (Figure S3), while absent in the normal urothelium, in accordance with previous reports (28,36). CK-positive cells were also found in all samples tested, characteristic of their epithelial origin.…”

Section: Stn Expression Of Urothelial Exfoliated Cells Correlates Witsupporting

confidence: 87%

“…In order to accurately identify urothelial ETCs and distinguish them from benign ones, we selected STn, a tumor associated antigen overexpressed in BC but absent in the healthy urothelium, as malignant biomarker (36). Indeed, STn has been directly associated with BC progression, metastatic potential of neoplastic cells, and decreased overall survival (28,36). More importantly, we recently reported STn expression in microfluidic-isolated CTCs from BC patients (28,29).…”

Section: Rigorous Identification Of Urothelial Etcs In Clinical Samplesmentioning

confidence: 99%

“…Indeed, STn has been directly associated with BC progression, metastatic potential of neoplastic cells, and decreased overall survival (28,36). More importantly, we recently reported STn expression in microfluidic-isolated CTCs from BC patients (28,29). For optimization purposes, we firstly used the invasive BC cell line MCR overexpressing STn antigen (MCR-STn), since STn levels in various non-transduced BC cells lines, including HT1376, are negligible (data not shown) (36).…”

Section: Rigorous Identification Of Urothelial Etcs In Clinical Samplesmentioning

confidence: 99%

“…Built on our previous work regarding the development of microfluidic platforms for the capture of BC CTCs (28,29), we herein report a new microfluidic chip for exfoliated tumor cell (ETC) enrichment from voided urine of BC patients. Importantly, ETCs are valuable sources of information regarding tumor biology and dynamics throughout the course of BC and treatment-follow up (35).…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic Analysis of Urothelial Exfoliated Cells in Bladder Cancer via Microfluidic Immunoassays: Sialyl-Tn as a Novel Biomarker in Liquid Biopsies

et al. 2020

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Bladder cancer is the most common malignancy of the urinary tract, having one of the highest recurrence rates and progression from non-muscle to muscle invasive bladder cancer that commonly leads to metastasis. Cystoscopy and urine cytology are the standard procedures for its detection but have limited clinical sensitivity and specificity. Herein, a microfluidic device, the UriChip, was developed for the enrichment of urothelial exfoliated cells from fresh and frozen urine, based on deformability and size, and the cancer-associated glycan Sialyl-Tn explored as a putative bladder cancer urinary biomarker. Spiking experiments with bladder cancer cell lines showed an isolation efficiency of 53%, while clinical sample analyses revealed retention of cells with various morphologies and sizes. in situ immunoassays demonstrated significantly higher number of Sialyl-Tn-positive cells in fresh and frozen voided urine from bladder cancer patients, compared to healthy individuals. Of note, urothelial exfoliated cells from cryopreserved urine sediments were also successfully isolated by the UriChip, and found to express significantly high levels of Sialyl-Tn. Remarkably, Sialyl-Tn expression is correlated with tumor stage and grade. Overall, our findings demonstrate the potential of UriChip and Sialyl-Tn to detect urothelial bladder cancer cells in follow-up and long-term retrospective studies.

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Section: Stn Expression Of Urothelial Exfoliated Cells Correlates Witsupporting

confidence: 87%

Section: Rigorous Identification Of Urothelial Etcs In Clinical Samplesmentioning

confidence: 99%

Section: Rigorous Identification Of Urothelial Etcs In Clinical Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Phenotypic Analysis of Urothelial Exfoliated Cells in Bladder Cancer via Microfluidic Immunoassays: Sialyl-Tn as a Novel Biomarker in Liquid Biopsies

et al. 2020

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“…In circulating tumor cells and metastatic lesions of bladder cancer, a higher expression of sialyl-Tn has been reported. This is indicative of a novel approach of isolating and characterizing bladder tumor cells rich in the sialyl-Tn glycan structure [93].…”

Section: Mechanistic Insights Of St6galnac-i In Different Bladder Tumormentioning

confidence: 90%

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Gupta

Leon

Rauth

et al. 2020

Cells

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Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell–cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.

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The current role and future directions of circulating tumor cells and circulating tumor DNA in urothelial carcinoma of the bladder

2018

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Sialyl-Tn identifies muscle-invasive bladder cancer basal and luminal subtypes facing decreased survival, being expressed by circulating tumor cells and metastases

Cited by 39 publications

References 13 publications

Phenotypic Analysis of Urothelial Exfoliated Cells in Bladder Cancer via Microfluidic Immunoassays: Sialyl-Tn as a Novel Biomarker in Liquid Biopsies

Phenotypic Analysis of Urothelial Exfoliated Cells in Bladder Cancer via Microfluidic Immunoassays: Sialyl-Tn as a Novel Biomarker in Liquid Biopsies

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

The current role and future directions of circulating tumor cells and circulating tumor DNA in urothelial carcinoma of the bladder

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