Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells

Cancer Lett. 2007 May 8;249(2):157-70. doi: 10.1016/j.canlet.2006.08.010. Epub 2006 Sep 11.

Abstract

The activation of an abnormal glycosylation pathway in cancer cells leads to the formation of the sialyl-Tn antigen, blocking regular carbohydrate chain elongation. Sialyl-Tn antigen is rarely expressed in normal tissues but is aberrantly expressed in a variety of carcinomas, where it constitutes a marker of poor prognosis. Although the clinical significance of sialyl-Tn is well characterized, a functional role for this glycan and its contribution to cancer progression remain to be elucidated. This study evaluates the capability of sialyl-Tn to modify processes like cell cycle, apoptosis, actin cytoskeleton dynamics, adhesion and motility on ECM components, cell-cell aggregation and invasion. De-novo expression of sialyl-Tn leads to major morphological and cell behavior alterations in gastric carcinoma cells which were reverted by specific antibody blockage. Sialyl-Tn antigen is able to modulate a malignant phenotype inducing a more aggressive cell behavior, such as decreased cell-cell aggregation and increased ECM adhesion, migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Antigens, Tumor-Associated, Carbohydrate / metabolism*
  • Apoptosis
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Adhesion
  • Cell Aggregation
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Mucin-1
  • Mucins / metabolism
  • Neoplasm Invasiveness
  • Phenotype
  • Sialyltransferases / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • Antigens, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • MUC1 protein, human
  • Mucin-1
  • Mucins
  • sialosyl-Tn antigen
  • Sialyltransferases
  • galactosyl-1-3-N-acetylgalactosaminyl-specific 2,6-sialyltransferase
  • CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase