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Alterations of O-glycan biosynthesis in human colon cancer tissues
J M Yang1, J C Byrd, B B Siddiki
1Department of Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract:
Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans is colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.
Insights
Colon cancer alters mucin O-glycan biosynthesis, with key enzyme activities changing. These changes suggest complex control mechanisms in cancer development.
Area of Science:
- Biochemistry
- Glycobiology
- Cancer Biology
Background:
- Human colon cancer exhibits altered mucin-type carbohydrate chains (O-glycans).
- Understanding the control of O-glycan biosynthesis is crucial for colon cancer research.
Purpose of the Study:
- To investigate glycosyltransferase and sulphotransferase activities in colon cancer.
- To elucidate the control mechanisms of O-glycan biosynthesis in colon cancer.
Main Methods:
- Analysis of homogenates from cancer and adjacent normal colon tissues of 20 patients.
- Assay of various glycosyltransferase and sulphotransferase activities.
- Correlation of enzyme activities with antigen levels, differentiation status, and clinical data.
Main Results:
- Several transferase activities were significantly altered in colon cancer tissue.
- Decreased activities observed for enzymes synthesizing O-glycan core 3, sialyl-Tn antigen, and core 1 structures.
- Increased activities found for enzymes synthesizing blood group H determinant and core 4 structures.
Conclusions:
- Colon cancer involves complex alterations in O-glycan biosynthesis pathways.
- Changes in specific glycosyltransferase and sulphotransferase activities contribute to altered O-glycan structures in colon cancer.
- These findings provide insights into the biochemical basis of O-glycan changes in colon cancer.