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

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.

• Authors: Sandra Pinho, Nuno T Marcos, Bibiana Ferreira, Ana S Carvalho, Maria J Oliveira, Filipe Santos-Silva, Anne Harduin-Lepers, Celso A Reis
• Journal: Cancer letters (Cancer Lett) Vol. 249 Issue 2 Pg. 157-70 (May 08 2007) ISSN: 0304-3835 [Print] Ireland
• PMID: 16965854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Antigens, Neoplasm (metabolism)
• Antigens, Tumor-Associated, Carbohydrate (metabolism)
• Apoptosis
• Carcinoma (metabolism, 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, pathology)