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Cellular and Molecular Life Sciences

, Volume 72, Issue 7, pp 1231–1248 | Cite as

Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense

  • Kayluz Frias Boligan
  • Circe Mesa
  • Luis Enrique Fernandez
  • Stephan von GuntenEmail author
Review

Abstract

Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a ‘microevolutionary’ process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display ‘enhanced self’ to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein–glycan interactions. A better understanding of tumor ‘glycan codes’ as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.

Keywords

Xeno-autosialylation Cancer glycosylation Cancer immunoediting Sialoglycans Altered branching Tumor immunosuppression 

Abbreviations

C2GnT

Core 2 β1,6-N-acetylglucosaminyltransferase

CEACAM-1

CEA-related cell adhesion molecule-1

CLR

C-type lectin receptors

CRD

Carbohydrate-recognition domains

DTDST

Diastrophic dysplasia sulfate transporter

FUT

Fucosyltransferase

ITIM

Immunoreceptor tyrosine-based inhibition motif

LOH

Loss of heterozygosity

MGAT3

Mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase

MGAT5

Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetylglucosaminyltransferase

MICA

MHC class I-related chain A

NGcGM3

N-Glycolyl GM3 ganglioside

NAcGM3

N-Acetyl GM3 ganglioside

NSCLC

Non-small cell lung cancer

ppGalNAcT

Polypeptide N-acetylgalactosyl transferase

PSGL-1

P-selectin glycoprotein ligand-1

SAMPs

Self-associated molecular patterns

Siglec

Sialic acid-binding immunoglobulin-like lectin

sT

Sialyl-T antigen

ST6Gal 1

Beta-galactoside α-2,6-sialyltransferase 1

sTn

Sialyl-Tn antigen

T

Thomsen-Friedenreich

TACA

Tumor-associated carbohydrate antigen

VSSP

Very small-sized proteoliposomes

Notes

Acknowledgments

Research by SVG is supported by the Swiss National Science Foundation (Grant No. 310030_135734), the Bulgarian-Swiss Research Program (BSRP) No. IZEBZO_142967, Swiss Cancer Research (KFS-3248-08-2013) and CSL Behring AG, Bern, Switzerland. The authors thank Aldona von Gunten for full illustration of Fig. 3 and assistance with Fig. 2.

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Kayluz Frias Boligan
    • 1
  • Circe Mesa
    • 2
  • Luis Enrique Fernandez
    • 3
  • Stephan von Gunten
    • 1
    Email author
  1. 1.Institute of PharmacologyUniversity of BernBernSwitzerland
  2. 2.Immunobiology DivisionCenter of Molecular ImmunologyHavanaCuba
  3. 3.Innovation DivisionCenter of Molecular ImmunologyHavanaCuba

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