<i>N</i>-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny

Kavanagh, Eoin; Halász, Melinda; Dowling, Paul; Withers, Jo; Lindsay, Sinéad; Higgins, Michaela J.; Irwin, Jane A.; Rudd, Pauline M.; Saldova, Radka; McCann, Amanda

doi:10.1039/d0mo00017e

Cited by 15 publications

(12 citation statements)

References 55 publications

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“…EV glycan signature in cancer ascites has been used for prognosis stratification of patients with colorectal and gastric cancers 20 , 31 . Monitoring glycosylation alterations of EVs secreted by chemotherapy-induced senescent TNBC cells provides valuable insight into the prediction of drug resistance and treatment efficacy 51 , 52 . Heavy N -glycosylation of PD-L1 on melanoma EVs facilitates the recognition and deactivation of PD-1 + CD8 + T cells, playing a vital role in inducing an immunosuppressive tumor microenvironment 23 , 53 .…”

Section: Discussionmentioning

confidence: 99%

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Li,

Zhang,

Liu

et al. 2024

Nat Commun

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Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

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Section: Discussionmentioning

confidence: 99%

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Li,

Zhang,

Liu

et al. 2024

Nat Commun

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“…Similarly, TrpC5 was also delivered to adriamycin-sensitive cells by sEVs but stimulated P-gp expression through the translocation of transcription factor, T-cells isoform c3 (NFATc3) [ 165 ]. In PTX-induced TNBC TIS, sEV glycoprotein profiling identified elevated P-gp, CD44, galectin-3, and glycogenin-1, suggesting that altered abundance of glycoproteins in sEVs could be a tool to evaluate the treatment efficacy of TNBC cells that are amenable to PTX chemotherapy [ 170 , 180 ].…”

Section: Sev Protein Biomarkers and Post Translational Modifications ...mentioning

confidence: 99%

Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis

Lee

Beretov

et al. 2023

Mol Cancer

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Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50–1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50–150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.

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“…Besides helping proteins to fold in the endoplasmic reticulum, glycosylation also facilitates ligand‐binding, mediates cell‐to‐cell communication, aids evasion of the immune system, and shields polypeptides from being recognized by antibodies or proteases. [ 46 ] In addition, glycans are also involved in the maturation of cells. [ 47 ] Aberrant glycosylation is an emerging hallmark of many cancers.…”

Section: Cd63 and Glycosylationmentioning

confidence: 99%

Revisiting the Role of CD63 as Pro‐Tumorigenic or Anti‐Tumorigenic Tetraspanin in Cancers and its Theragnostic Implications

2023

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Cluster of differentiation antigen 63 (CD63) belongs to a superfamily of proteins, usually defined as tetraspanins which are known to transverse the bilayer membranes four times. The expression of CD63 has been shown to get altered in several cancers, where it has been demonstrated to act as both a tumor promoter and tumor suppressor. The present review describes the mechanism of how CD63 promotes tumor formation in certain cancer types while inhibiting in some other specific cancers. Glycosylation, a post-translational process plays a significant role in regulating the expression and function of these membrane proteins. Being a crucial exosomal flag protein, CD63 has been found to get involved in endosomal cargo sorting as well as the production of extracellular vesicles. Increased expression of exosomal CD63 derived from advanced tumors has demonstrated its role in promoting metastasis. CD63 also regulates the characteristic and function of stem cells on which they get expressed. This particular tetraspanin has been discovered to participate in gene fusion to perform distinctive roles in certain specific cancer types like breast cancer and pigmented epithelioid melanocytoma. Furthermore, this review mentions twelve different microRNAs obtained from miRDB that might target CD63. A few theragnostic uses of this membrane protein are also discussed. Thereby, the review indicates that further studies on CD63 might prove it to be an effective therapeutic target in different cancers in the coming future.

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N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny

Abstract: Therapeutic-induced-senescent (TIS) Cal51 TNBC cells display differential N-glycan moieties compared to non-senescent cells, depending on cellular location and EV progeny.

Cited by 15 publications

References 55 publications

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis

Revisiting the Role of CD63 as Pro‐Tumorigenic or Anti‐Tumorigenic Tetraspanin in Cancers and its Theragnostic Implications

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