Exploring sialyl-Tn expression in microfluidic-isolated circulating tumour cells: A novel biomarker and an analytical tool for precision oncology applications

Neves, Manuel; Azevedo, Rita; Lima, Luís; Oliveira, Marta I.; Peixoto, Andreia; Ferreira, Dylan; Soares, Janine; Fernandes, Elisabete; Gaiteiro, Cristiana; Palmeira, Carlos; Cotton, Sofia; Mereiter, Stefan; Campos, Diana; Afonso, Luís Pedro; Ribeiro, Ricardo; Fraga, Avelino; Tavares, Ana; Mansinho, Hélder; Monteiro, Eurico; Videira, Paula A.; Freitas, P. P.; Reis, Celso A.; Santos, Lúcio Lara; Diéguez, Lorena; Ferreira, José Alexandre

doi:10.1016/j.nbt.2018.09.004

Cited by 31 publications

(27 citation statements)

References 61 publications

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“…In addition to colorectal carcinoma, ST6GalNAc-I expression has been found to be elevated in cancer stem cells (CSC) populations [101]. The authors indicated an association of CSC markers with higher incidence of sialyl-Tn expression in these CSCs.…”

Section: Clinical Implications Of St6galnac-i In Colon Carcinomamentioning

confidence: 99%

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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Section: Clinical Implications Of St6galnac-i In Colon Carcinomamentioning

confidence: 99%

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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“…However, novel diagnostic tools with better affinity and specificity are needed. It has been shown that more than 90% of isolated CTCs metastatic bladder and colorectal cancers can overexpress the STn antigen, significantly higher than EpCAM-based detection (27) 6. SA-MIPs were pre-incubated with the SA-derivatives ME0970 or ME1057, respectively and analyzed with flow cytometry.…”

Section: Discussionmentioning

confidence: 97%

Sialic acid as a biomarker studied in breast cancer cells using fluorescent molecularly imprinted polymers, MIPs

El-Schich¹,

Zhang²,

Göransson³

et al. 2020

Preprint

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Sialylations are post-translational modifications of proteins and lipids that play important roles in many cellular events, including cell-cell interactions, proliferation and migration. Tumor cells express high levels of sialic acid (SA), which are often associated with the increased invasive potential in clinical tumors correlating with poor prognosis. To overcome the lack of natural SA-receptors, such as antibodies and lectins with high enough specificity and sensitivity, we have used molecularly imprinted polymers (MIPs), or “plastic antibodies”, as nanoprobes. Since high expression of EpCAM in primary tumors often is associated with proliferation and a more aggressive phenotype, the expression and of epithelial cell adhesion molecule (EpCAM) CD44 was initially analyzed. The SA-MIPs were used here for the detection of SA on the cell surface of breast cancer cells. Lectins that specifically bind to the α-2,3 SA and α-2,6 SA variants, respectively, were used for analysis of SA expression with both flow cytometry and confocal microscopy. Here we show a correlation of EpCAM and SA expression when using the SA-MIPs for detection of SA. We also demonstrate the binding pattern of the SA-MIPs on the breast cancer cell lines using confocal microscopy. Pre-incubation of the SA-MIPs with SA-derivatives as inhibitors could reduce the binding of the SA-MIPs to the tumor cells, indicating the specificity of the SA-MIPs. In conclusion, the SA-MIPs may be a new powerful tool in the SA-analysis of breast cancer cells.

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“…FFPE tissue sections from patients with BC were screened for STn staining using the streptavidin/biotin peroxidase method with the anti-STn antibody, as previously described (29).…”

Section: Tissue Immunohistochemistrymentioning

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%

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

et al. 2020

Self Cite

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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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Exploring sialyl-Tn expression in microfluidic-isolated circulating tumour cells: A novel biomarker and an analytical tool for precision oncology applications

Cited by 31 publications

References 61 publications

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

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

Sialic acid as a biomarker studied in breast cancer cells using fluorescent molecularly imprinted polymers, MIPs

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

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