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The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression.

ABSTRACT: Glycans are part of the essential components of a cell. These compounds play a fundamental role in several physiopathological processes, including cell differentiation, adhesion, motility, signal transduction, host-pathogen interactions, tumor cell invasion, and metastasis development. Glycans are also able to exert control over the changes in tumor immunogenecity, interfering with tumor editing events and leading to immune-resistant cancer cells. The involvement of glycans in cancer progression is related to glycosylation alterations. Understanding such changes is, therefore, extremely useful to set the stage for their use as biomarkers, improving the diagnostics and therapeutic strategies. Herein, we discuss the basis of how modifications in glycosylation patterns may contribute to cancer genesis and progression as well as their importance in oncology field.

SUBMITTER: Nardy AF

PROVIDER: S-EPMC4783415 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression.

Nardy Ana Flávia Fernandes Ribas AF Freire-de-Lima Leonardo L Freire-de-Lima Célio Geraldo CG Morrot Alexandre A

Frontiers in oncology 20160309

Glycans are part of the essential components of a cell. These compounds play a fundamental role in several physiopathological processes, including cell differentiation, adhesion, motility, signal transduction, host-pathogen interactions, tumor cell invasion, and metastasis development. Glycans are also able to exert control over the changes in tumor immunogenecity, interfering with tumor editing events and leading to immune-resistant cancer cells. The involvement of glycans in cancer progression ...[more]

PMID: 27014629

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Project description:The Ebola Virus (EBOV) glycoprotein (GP) sterically shields cell-membrane ligands to immune receptors such as human leukocyte antigen class-1 (HLA-I) and MHC class I polypeptide-related sequence A (MICA), thus mediating immunity evasion. It was suggested that the abundant N-glycosylation of the EBOV-GP is involved in this steric shielding. We aimed to characterize (i) the GP N-glycosylation sites contributing to the shielding, and (ii) the effect of mutating these sites on immune subversion by the EBOV-GP. The two highly glycosylated domains of GP are the mucin-like domain (MLD) and the glycan cap domain (GCD) with three and six N-glycosylation sites, respectively. We mutated the N-glycosylation sites either in MLD or in GCD or in both domains. We showed that the glycosylation sites in both the MLD and GCD domains contribute to the steric shielding. This was shown for the steric shielding of either HLA-I or MICA. We then employed the fluorescence resonance energy transfer (FRET) method to measure the effect of N-glycosylation site removal on the distance in the cell membrane between the EBOV-GP and HLA-I (HLA.A*0201 allele). We recorded high FRET values for the interaction of CFP-fused HLA.A*0201 and YFP-fused EBOV-GP, demonstrating the very close distance (<10 nm) between these two proteins on the cell membrane of GP-expressing cells. The co-localization of HLA-I and Ebola GP was unaffected by the disruption of steric shielding, as the removal of N-glycosylation sites on Ebola GP revealed similar FRET values with HLA-I. However, these mutations directed to N-glycosylation sites had restored immune cell function otherwise impaired due to steric shielding over immune cell ligands by WT Ebola GP. Overall, we showed that the GP-mediated steric shielding aimed to impair immune function is facilitated by the N-glycans protruding from its MLD and GCD domains, but these N-glycans are not controlling the close distance between GP and its shielded proteins.

Dataset Information

The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression.

Publications

The Sweet Side of Immune Evasion: Role of Glycans in the Mechanisms of Cancer Progression.

Similar Datasets

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