Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells.
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.
Pinho
Sandra
S
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias, s/n 4200-465 Porto, Portugal.
Marcos
Nuno T
NT
Ferreira
Bibiana
B
Carvalho
Ana S
AS
Oliveira
Maria J
MJ
Santos-Silva
Filipe
F
Harduin-Lepers
Anne
A
Reis
Celso A
CA
D000951:Antigens, Neoplasm / Q000378:metabolism; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D018396:Mucin-1; D009077:Mucins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype; D012799:Sialyltransferases / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; C055491:sialosyl-Tn antigen; D012799:Sialyltransferases; C088391:galactosyl-1-3-N-acetylgalactosaminyl-specific 2,6-sialyltransferase; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase