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.