Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Beckwith, Donella; Čudić, Mare

doi:10.1016/j.smim.2020.101389

Cited by 85 publications

(87 citation statements)

References 169 publications

(210 reference statements)

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“…Due to their relevance, incomplete or truncated glycan structures, often covered by sialic acid and commonly known as tumor-associated carbohydrate antigens (TACA), have been studied (94). These antigens have already been seen to be overexpressed in different cancer types, such as breast, pancreas, bladder, and colon cancer (95)(96)(97)(98).…”

Section: G-np Applications In Immunotherapy and Vaccinesmentioning

confidence: 99%

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery

Torres-Pérez

Pedraza-Escalona

et al. 2020

Front. Oncol.

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Nanoparticles (NPs) are novel platforms that can carry both cancer-targeting molecules and drugs to avoid severe side effects due to nonspecific drug delivery in standard chemotherapy treatments. Cancer cells are characterized by abnormal membranes, metabolic changes, the presence of lectin receptors, glucose transporters (GLUT) overexpression, and glycosylation of immune receptors of programmed death on cell surfaces. These characteristics have led to the development of several strategies for cancer therapy, including a large number of carbohydrate-modified NPs, which have become desirable for use in cell-selective drug delivery systems because they increase nanoparticle-cell interactions and uptake of carried drugs. Currently, the potential of NP glycosylation to enhance the safety and efficacy of carried therapeutic antitumor agents has been widely acknowledged, and much information is accumulating in this field. This review seeks to highlight recent advances in NP stabilization, toxicity reduction, and pharmacokinetic improvement and the promising potential of NP glycosylation from the perspective of molecular mechanisms described for drug delivery systems for cancer therapy. From preclinical proof-of-concept to demonstration of therapeutic value in the clinic, the challenges and opportunities presented by glycosylated NPs, with a focus on their applicability in the development of nanodrugs, are discussed in this review.

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Section: G-np Applications In Immunotherapy and Vaccinesmentioning

confidence: 99%

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery

Torres-Pérez

Pedraza-Escalona

et al. 2020

Front. Oncol.

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“…Certain glycans that show increased expression in tumor tissues as compared to normal tissues are referred to as Tumor-Associated Carbohydrate Antigens (TACAs) [ 7 ]. Many TACAs are in fact truncated glycan structures resulting from incomplete glycan biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

Pirro

Mohammed

Vliet

et al. 2020

IJMS

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Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL-binding glycoproteins in two high-MGL-binding CRC cells lines, HCT116 and HT29. However, we failed to detect the presence of O-linked Tn and STn glycans on most CRC glycoproteins recognized by MGL. We therefore investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines. Finally, we highlighted both common and cell-specific processes associated with a high-MGL-binding phenotype, such as differential levels of enzymes involved in protein glycosylation, and a transcriptional factor (CDX-2) involved in their regulation.

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“…Protein glycosylation is known to have important effects in cell biological processes (such as proliferation, adhesion, differentiation, cell-cell interaction and immune response), and abnormal glycosylation is considered to be a hallmark of cancer [15] . Certain glycans with increased expression in tumor tissues compared to normal tissues are known as tumor-associated carbohydrate antigens (TACA) [16] . During tumor development, immune cells can detect the presence of TACA, which can enhance or weaken the immune response depending on the nature of the interaction [17] .…”

Section: Discussionmentioning

confidence: 99%

CLEC10A is a Potential Prognostic Biomarker and Immune Regulator of Tumor Microenvironment in Breast Cancer

Jiang

Wang

et al. 2021

Preprint

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The communication between tumor cells and immune cells influences the ecology of the tumor microenvironment in breast cancer, as well as the disease progression and clinical outcome. The aim of this study was to investigate the prognostic value of the immunomodulatory factor CLEC10A in breast cancer. We applied the CIBERSORT and ESTIMATE calculation methods to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal components in 1053 BRCA cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, CLEC10A was identified as a prognostic factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that CLEC10A expression was negatively correlated with the clinical pathologic characteristics (age, clinical stage) and positively correlated with survival of BRCA patients. Gene set enrichment analysis (GSEA) showed that genes in the high CLEC10A expression group were mainly enriched in immune-related activities. Genes in the low CLEC10A expression group were enriched in biochemical functions. CIBERSORT analysis of the proportion of TICs revealed that Macrophages M1, B cells memory, B cells naive, T cells CD4+ memory activated, T cells CD8+, and T cells gamma delta were positively correlated with CLEC10A expression, and Macrophages M0, Macrophages M2, Neutrophils, and NK cells resting were positively correlated with CLEC10A expression was negatively correlated, suggesting that CLEC10A may be an important factor in the immune regulation of the tumor microenvironment, especially in mediating the anti-tumor immune response of tumor-infiltrating immune cells at the tumor initiation stage. Therefore, CLEC10A expression may contribute to the prognosis of BRCA patients and provide a new idea for the immunotherapy of BRCA.

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Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design

Cited by 85 publications

References 169 publications

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

CLEC10A is a Potential Prognostic Biomarker and Immune Regulator of Tumor Microenvironment in Breast Cancer

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