Pathways of Mucin O-Glycosylation in Normal and Malignant Rat Colonic Epithelial Cells Reveal a Mechanism for Cancer-Associated Sialyl-Tn Antigen Expression
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I. Brockhausen J. Yang
Abstract
The SialylTn antigen (Sialyl?Ser/Thr) is expressed as a cancerassociated antigen on the surface of cancer cells. Its presence is associated with a poor prognosis in patients with colorectal and other cancers. We previously reported that SialylTn expression in LSC human colon cancer cells could be explained by a specific lack of the activity of core 1 ?3-Galtransferase (Brockhausen et al., Glycoconjugate J. 15, 595 603, 1998) and an inability to synthesize the common Oglycan core structures. To support this mechanism, or find other mechanisms to explain SialylTn antigen expression, we investigated the Oglycosylation pathways in clonal rat colon cancer cell lines that were selected for positive or negative expression of SialylTn antigen, and compared these pathways to those in normal rat colonic mucosa. Normal rat colonic mucosa had very active glycosyltransferases synthesizing Oglycan core structures 1 to 4. Several sialyl, sulfo and fucosyltransferases were also active. An M type core 2 ?6-GlcNActransferase was found to be present in rat colon mucosa and all of the rat colon cancer cells. Oglycosylation pathways in rat colon cancer cells were significantly different from normal rat colonic mucosa; for example, rat colon cancer cells lost the ability to synthesize Oglycan core 3. All rat colon cancer cell lines, regardless of the SialylTn phenotype, expressed glycosyltransferases assembling complex Oglycans of core 1 and core 2 structures (unlike human LSC colon cancer cells which lack core 1 ?3-Galtransferase activity). It was the activity of CMPsialic acid:GalNAcmucin ?6-sialyltransferase that coincided with SialylTn expression. SialylTn negative cells had a several fold higher activity of core 2 ?6-GlcNActransferase which synthesizes complex Oglycans that may mask adjacent SialylTn epitopes. The results suggest a new mechanism controlling SialylTn expression in cancer cells.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
Artikel in diesem Heft
- Highlight: Glycobiology
- O-Glycosylation of the Mucin Type
- Glycoproteins from Insect Cells: Sialylated or Not?
- Congenital Disorders of Glycosylation: Glycosylation Defects in Man and Biological Models for Their Study
- Mitochondrial Single-Stranded DNA-Binding Proteins: in Search for New Functions
- Do Rodent and Human Brains Have Different N-Glycosylation Patterns?
- The Liver Flukes Fasciola gigantica and Fasciola hepatica Express the Leucocyte Cluster of Differentiation Marker CD77 (Globotriaosylceramide) in Their Tegument
- Cloning and Expression of Drosophila melanogaster UDP-GlcNAc:?-3-D-Mannoside ? 1,2-N-Acetylglucosaminyltransferase I
- Pathways of Mucin O-Glycosylation in Normal and Malignant Rat Colonic Epithelial Cells Reveal a Mechanism for Cancer-Associated Sialyl-Tn Antigen Expression
- 6-O-Sulfo De-N-Acetylsialyl Lewis X as a Novel High-Affinity Ligand for Human L-Selectin: Total Synthesis and Structural Characterization
- Segregation of Gangliosides GM1 and GD3 on Cell Membranes, Isolated Membrane Rafts, and Defined Supported Lipid Monolayers
- Structural Characterization of Fucose-Containing Oligosaccharides by High-Performance Liquid Chromatography and Matrix-Assisted Laser Desorption/ Ionization Time-of-Flight Mass Spectrometry
- Anencephaly: Structural Characterization of Gangliosides in Defined Brain Regions
- Acidic Glycerol Lipids of Trichomonas vaginalis and Tritrichomonas foetus
- Stimulation of Acid Sphingomyelinase Activity by Lysosomal Lipids and Sphingolipid Activator Proteins
- Biosynthesis of N-Acetylneuraminic Acid in Cells Lacking UDP-N-Acetylglucosamine 2-Epimerase/ N-Acetylmannosamine Kinase
- Synthesis of Nucleotide-Activated Oligosaccharides by ?-Galactosidase from Bacillus circulans
- Elucidation of the Role of Functional Amino Acid Residues of the Small Sialidase from Clostridium perfringens by Site-Directed Mutagenesis
- Biosynthesis of Lipid-Linked Oligosaccharides in Yeast: the ALG3 Gene Encodes the Dol-P-Man:Man5GlcNAc2-PP-Dol Mannosyltransferase
- Intra- and Intermolecular Triplex DNA Formation in the Murine c-myb Proto-Oncogene Promoter Are Inhibited by Mithramycin
- Experimental Regulation of STAT Gene Expression Reveals an Involvement of STAT5 in Interleukin-4-Driven Cell Proliferation
Artikel in diesem Heft
- Highlight: Glycobiology
- O-Glycosylation of the Mucin Type
- Glycoproteins from Insect Cells: Sialylated or Not?
- Congenital Disorders of Glycosylation: Glycosylation Defects in Man and Biological Models for Their Study
- Mitochondrial Single-Stranded DNA-Binding Proteins: in Search for New Functions
- Do Rodent and Human Brains Have Different N-Glycosylation Patterns?
- The Liver Flukes Fasciola gigantica and Fasciola hepatica Express the Leucocyte Cluster of Differentiation Marker CD77 (Globotriaosylceramide) in Their Tegument
- Cloning and Expression of Drosophila melanogaster UDP-GlcNAc:?-3-D-Mannoside ? 1,2-N-Acetylglucosaminyltransferase I
- Pathways of Mucin O-Glycosylation in Normal and Malignant Rat Colonic Epithelial Cells Reveal a Mechanism for Cancer-Associated Sialyl-Tn Antigen Expression
- 6-O-Sulfo De-N-Acetylsialyl Lewis X as a Novel High-Affinity Ligand for Human L-Selectin: Total Synthesis and Structural Characterization
- Segregation of Gangliosides GM1 and GD3 on Cell Membranes, Isolated Membrane Rafts, and Defined Supported Lipid Monolayers
- Structural Characterization of Fucose-Containing Oligosaccharides by High-Performance Liquid Chromatography and Matrix-Assisted Laser Desorption/ Ionization Time-of-Flight Mass Spectrometry
- Anencephaly: Structural Characterization of Gangliosides in Defined Brain Regions
- Acidic Glycerol Lipids of Trichomonas vaginalis and Tritrichomonas foetus
- Stimulation of Acid Sphingomyelinase Activity by Lysosomal Lipids and Sphingolipid Activator Proteins
- Biosynthesis of N-Acetylneuraminic Acid in Cells Lacking UDP-N-Acetylglucosamine 2-Epimerase/ N-Acetylmannosamine Kinase
- Synthesis of Nucleotide-Activated Oligosaccharides by ?-Galactosidase from Bacillus circulans
- Elucidation of the Role of Functional Amino Acid Residues of the Small Sialidase from Clostridium perfringens by Site-Directed Mutagenesis
- Biosynthesis of Lipid-Linked Oligosaccharides in Yeast: the ALG3 Gene Encodes the Dol-P-Man:Man5GlcNAc2-PP-Dol Mannosyltransferase
- Intra- and Intermolecular Triplex DNA Formation in the Murine c-myb Proto-Oncogene Promoter Are Inhibited by Mithramycin
- Experimental Regulation of STAT Gene Expression Reveals an Involvement of STAT5 in Interleukin-4-Driven Cell Proliferation
