Cell surface alpha 2,6 sialylation affects adhesion of breast carcinoma cells

Exp Cell Res. 2002 May 15;276(1):101-10. doi: 10.1006/excr.2002.5521.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma / enzymology*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Adhesion*
  • Cell Membrane / enzymology
  • Cell Membrane / metabolism
  • Cell Movement
  • Clone Cells
  • Extracellular Matrix Proteins / pharmacology
  • Female
  • Humans
  • N-Acetylneuraminic Acid / metabolism
  • Neoplasm Invasiveness
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • RNA, Messenger / biosynthesis
  • Sialyltransferases / genetics
  • Sialyltransferases / metabolism*
  • Tumor Cells, Cultured

Substances

  • Extracellular Matrix Proteins
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Messenger
  • Sialyltransferases
  • beta-D-galactoside alpha 2-6-sialyltransferase
  • N-Acetylneuraminic Acid