Cell surface alpha 2,6 sialylation affects adhesion of breast carcinoma cells.
Tumor-associated alterations of cell surface glycosylation play a crucial role in the adhesion and metastasis of carcinoma cells. The aim of this study was to examine the effect of alpha 2,6-sialylation on the adhesion properties of breast carcinoma cells. To this end mammary carcinoma cells, MDA-MB-435, were sense-transfected with sialyltransferase ST6Gal-I cDNA or antisense-transfected with a part of the ST6Gal-I sequence. Sense transfectants showed an enhanced ST6Gal-I mRNA expression and enzyme activity and an increased binding of the lectin Sambucus nigra agglutinin (SNA), specific for alpha 2,6-linked sialic acid. Transfection with ST6Gal-I in the antisense direction resulted in less enzyme activity and SNA reactivity. A sense-transfected clone carrying increased amounts of alpha 2,6-linked sialic acid adhered preferentially to collagen IV and showed reduced cell-cell adhesion and enhanced invasion capacity. In contrast, antisense transfection led to less collagen IV adhesion but enhanced homotypic cell-cell adhesion. In another approach, inhibition of ST6Gal-I enzyme activity by application of soluble antisense-oligodeoxynucleotides was studied. Antisense treatment resulted in reduced ST6 mRNA expression and cell surface 2,6-sialylation and significantly decreased collagen IV adhesion. Our results suggest that cell surface alpha 2,6-sialylation contributes to cell-cell and cell-extracellular matrix adhesion of tumor cells. Inhibition of sialytransferase ST6Gal-I by antisense-oligodeoxynucleotides might be a way to reduce the metastatic capacity of carcinoma cells.
Lin
Shaoqiang
S
Department of Surgery and Surgical Oncology, Robert-Rössle-Klinik, Max-Delbrück-Center for Molecular Medicine, Charité, Campus-Buch, 13125 Berlin, Germany.
Kemmner
Wolfgang
W
Grigull
Sabine
S
Schlag
Peter M
PM
D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002465:Cell Movement; D002999:Clone Cells; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005260:Female; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D016326:Extracellular Matrix Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase