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PMID: 16741504 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions.

EMBO reports ·Vol. 7 ·No. 6 ·2006-06-00 ·Pages 599-604

Brockhausen I

Abstract

The glycoproteins of tumour cells are often abnormal, both in structure and in quantity. In particular, the mucin-type O-glycans have several cancer-associated structures, including the T and Tn antigens, and certain Lewis antigens. These structural changes can alter the function of the cell, and its antigenic and adhesive properties, as well as its potential to invade and metastasize. Cancer-associated mucin antigens can be exploited in diagnosis and prognosis, and in the development of cancer vaccines. The activities and Golgi localization of glycosyltransferases are the basis for the glycodynamics of cancer cells, and determine the ranges and amounts of specific O-glycans produced. This review focuses on the glycosyltransferases of colon and breast cancer cells that determine the pathways of mucin-type O-glycosylation, and the proposed functional and pathological consequences of altered O-glycans.

MeSH Terms
Breast Neoplasms/enzymology,metabolism,pathology Colonic Neoplasms/enzymology,metabolism,pathology Female Glycosylation Glycosyltransferases/metabolism Humans Mucins/chemistry,metabolism Polysaccharides/chemistry,metabolism
Chemicals
Mucins Polysaccharides Glycosyltransferases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Brockhausen Inka
Department of Medicine and Biochemistry, Human Mobility Research Centre, Queen's University, Kingston General Hospital, Angada 1, Kingston, Ontario K7L 2V7, Canada. [email protected]
References (57)
57 references, click to expand
  1. Pathways of mucin O-glycosylation in normal and malignant rat colonic epithelial cells reveal a mechanism for cancer-associated Sialyl-Tn antigen expression.
    Biol Chem. 2001 Feb;382(2):219-32 PMID: 11308020
  2. Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases.
    Gut. 2000 Mar;46(3):359-66 PMID: 10673297
  3. O-linked glycosylation in the mammary gland: changes that occur during malignancy.
    J Mammary Gland Biol Neoplasia. 2001 Jul;6(3):355-64 PMID: 11547903
  4. Tumor necrosis factor alpha increases the expression of glycosyltransferases and sulfotransferases responsible for the biosynthesis of sialylated and/or sulfated Lewis x epitopes in the human bronchial mucosa.
    J Biol Chem. 2002 Jan 4;277(1):424-31 PMID: 11679593
  5. Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide galNAc N-acetylgalactosaminyl transferase-3 in relation to differentiation and prognosis in patients with colorectal carcinoma.
    Cancer. 2002 Apr 1;94(7):1939-46 PMID: 11932895
  6. Dynamic regulation of T cell immunity by CD43.
    J Immunol. 2002 Jun 15;168(12):6022-31 PMID: 12055210
  7. Altered mucin expression in the gastrointestinal tract: a review.
    J Cell Mol Med. 2001 Jul-Sep;5(3):327-51 PMID: 12067494
  8. All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases.
    Glycobiology. 2003 Jan;13(1):1R-16R PMID: 12634319
  9. Sulphotransferases acting on mucin-type oligosaccharides.
    Biochem Soc Trans. 2003 Apr;31(2):318-25 PMID: 12653628
  10. Aberrant O-glycosylation inhibits stable expression of dysadherin, a carcinoma-associated antigen, and facilitates cell-cell adhesion.
    Glycobiology. 2003 Jul;13(7):521-7 PMID: 12672699
  11. Glycan-dependent leukocyte adhesion and recruitment in inflammation.
    Curr Opin Cell Biol. 2003 Oct;15(5):531-8 PMID: 14519387
  12. Mucins in cancer: protection and control of the cell surface.
    Nat Rev Cancer. 2004 Jan;4(1):45-60 PMID: 14681689
  13. Glycodynamics of mucin biosynthesis in gastrointestinal tumor cells.
    Adv Exp Med Biol. 2003;535:163-88 PMID: 14714895
  14. Sialylated core 1 based O-linked glycans enhance the growth rate of mammary carcinoma cells in MUC1 transgenic mice.
    Int J Oncol. 2004 Oct;25(4):937-43 PMID: 15375543
  15. The effect of TNF-alpha on glycosylation pathways in bovine synoviocytes.
    Biochem Cell Biol. 2004 Oct;82(5):559-68 PMID: 15499384
  16. Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin.
    Cancer Res. 1983 Nov;43(11):5489-92 PMID: 6193872
  17. Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate.
    Cancer Res. 1990 Jul 15;50(14):4308-14 PMID: 2364387
  18. Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients.
    Cancer. 1990 Nov 1;66(9):1960-6 PMID: 2224793
  19. Control of mucin synthesis: the peptide portion of synthetic O-glycopeptide substrates influences the activity of O-glycan core 1 UDPgalactose:N-acetyl-alpha-galactosaminyl-R beta 3-galactosyltransferase.
    Biochemistry. 1990 Nov 6;29(44):10206-12 PMID: 2125490
  20. Induction of alpha-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice.
    Cancer Res. 1991 Mar 1;51(5):1406-11 PMID: 1997178
  21. Inhibition of selectin-dependent tumor cell adhesion to endothelial cells and platelets by blocking O-glycosylation of these cells.
    Biochem Biophys Res Commun. 1992 Feb 14;182(3):1288-95 PMID: 1371678
  22. Mucins bearing the cancer-associated sialosyl-Tn antigen mediate inhibition of natural killer cell cytotoxicity.
    Cancer Res. 1992 Sep 1;52(17):4741-6 PMID: 1511439
  23. Involvement of histo-blood-group antigens in the susceptibility of colon carcinoma cells to natural killer-mediated cytotoxicity.
    Int J Cancer. 1992 Oct 21;52(4):609-18 PMID: 1399144
  24. Episialin (MUC1) inhibits cytotoxic lymphocyte-target cell interaction.
    J Immunol. 1993 Jul 15;151(2):767-76 PMID: 7687622
  25. Increased expression of sialyl Lewisx antigen correlates with poor survival in patients with colorectal carcinoma: clinicopathological and immunohistochemical study.
    Cancer Res. 1993 Aug 1;53(15):3632-7 PMID: 8101764
  26. cis-Golgi resident proteins and O-glycans are abnormally compartmentalized in the RER of colon cancer cells.
    J Cell Sci. 1993 Jul;105 ( Pt 3):819-30 PMID: 7691849
  27. Biosynthetic basis of incompatible histo-blood group A antigen expression: anti-A transferase antibodies reactive with gastric cancer tissue of type O individuals.
    Cancer Res. 1993 Nov 15;53(22):5494-500 PMID: 8221689
  28. O-glycan biosynthesis in human colorectal adenoma cells during progression to cancer.
    Eur J Biochem. 1994 Jun 1;222(2):415-24 PMID: 8020479
  29. Subcellular localization of the UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-mediated O-glycosylation reaction in the submaxillary gland.
    Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8935-9 PMID: 8090748
  30. Synthesis of O-glycan core 3: characterization of UDP-GlcNAc: GalNAc-R beta 3-N-acetyl-glucosaminyltransferase activity from colonic mucosal tissues and lack of the activity in human cancer cell lines.
    Glycobiology. 1995 May;5(3):351-7 PMID: 7655172
  31. T/Tn antigen vaccine is effective and safe in preventing recurrence of advanced breast carcinoma.
    Cancer Detect Prev. 1995;19(4):374-80 PMID: 7553680
  32. Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells.
    Eur J Biochem. 1995 Oct 15;233(2):607-17 PMID: 7588808
  33. Enhanced sialylation of mucin-associated carbohydrate structures in human colon cancer metastasis.
    Gastroenterology. 1996 May;110(5):1354-67 PMID: 8613039
  34. Fucosyltransferase III and sialyl-Le(x) expression correlate in cultured colon carcinoma cells but not in colon carcinoma tissue.
    Glycoconj J. 1996 Oct;13(5):727-33 PMID: 8909999
  35. Altered mRNA expression of specific molecular species of fucosyl- and sialyl-transferases in human colorectal cancer tissues.
    Int J Cancer. 1997 May 16;71(4):556-64 PMID: 9178808
  36. Carcinoma-associated expression of core 2 beta-1,6-N-acetylglucosaminyltransferase gene in human colorectal cancer: role of O-glycans in tumor progression.
    Cancer Res. 1997 Dec 1;57(23):5201-6 PMID: 9393734
  37. Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus.
    J Cell Sci. 1998 Jan;111 ( Pt 1):45-60 PMID: 9394011
  38. Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa.
    Glycoconj J. 1998 Jan;15(1):29-35 PMID: 9530954
  39. Gene expression of fucosyl- and sialyl-transferases which synthesize sialyl Lewisx, the carbohydrate ligands for E-selectin, in human breast cancer.
    Int J Oncol. 1998 May;12(5):1157-64 PMID: 9538143
  40. Up-regulation of a set of glycosyltransferase genes in human colorectal cancer.
    Lab Invest. 1998 Jul;78(7):797-811 PMID: 9690558
  41. Single glycosyltransferase, core 2 beta1-->6-N-acetylglucosaminyltransferase, regulates cell surface sialyl-Lex expression level in human pre-B lymphocytic leukemia cell line KM3 treated with phorbolester.
    J Biol Chem. 1998 Oct 9;273(41):26779-89 PMID: 9756922
  42. Glycoproteins and their relationship to human disease.
    Acta Anat (Basel). 1998;161(1-4):36-78 PMID: 9780351
  43. Enzymatic basis for sialyl-Tn expression in human colon cancer cells.
    Glycoconj J. 1998 Jun;15(6):595-603 PMID: 9881766
  44. Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family.
    Glycobiology. 1999 Jan;9(1):43-52 PMID: 9884405
  45. Control of O-glycan branch formation. Molecular cloning of human cDNA encoding a novel beta1,6-N-acetylglucosaminyltransferase forming core 2 and core 4.
    J Biol Chem. 1999 Feb 19;274(8):4504-12 PMID: 9988682
  46. Molecular mechanisms of expression of Lewis b antigen and other type I Lewis antigens in human colorectal cancer.
    Glycobiology. 1999 Jun;9(6):607-16 PMID: 10336994
  47. Stable expression of sialyl-Tn antigen in T47-D cells induces a decrease of cell adhesion and an increase of cell migration.
    Breast Cancer Res Treat. 2005 Mar;90(1):77-84 PMID: 15770530
  48. Siglecs in innate immunity.
    Curr Opin Pharmacol. 2005 Aug;5(4):431-7 PMID: 15955740
  49. The cooperation between two CD4 T cells induces tumor protective immunity in MUC.1 transgenic mice.
    J Immunol. 2005 Nov 15;175(10):6551-9 PMID: 16272309
  50. Siglecs--the major subfamily of I-type lectins.
    Glycobiology. 2006 Jan;16(1):1R-27R PMID: 16014749
  51. O-glycosylated versus non-glycosylated MUC1-derived peptides as potential targets for cytotoxic immunotherapy of carcinoma.
    Clin Exp Immunol. 2006 Jan;143(1):139-49 PMID: 16367945
  52. The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer.
    J Biol Chem. 2006 Feb 10;281(6):3586-94 PMID: 16319059
  53. UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker.
    J Histochem Cytochem. 2006 Mar;54(3):317-28 PMID: 16260590
  54. UDP-Gal: GlcNAc-R beta1,4-galactosyltransferase--a target enzyme for drug design. Acceptor specificity and inhibition of the enzyme.
    Glycoconj J. 2006 Nov;23(7-8):525-41 PMID: 17006644
  55. An alpha2,3 sialyltransferase (ST3Gal I) is elevated in primary breast carcinomas.
    Glycobiology. 1999 Dec;9(12):1307-11 PMID: 10561455
  56. Pathways of O-glycan biosynthesis in cancer cells.
    Biochim Biophys Acta. 1999 Dec 6;1473(1):67-95 PMID: 10580130
  57. Overexpression of sialyltransferase CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-Sialyltransferase is related to poor patient survival in human colorectal carcinomas.
    Cancer Res. 2001 Jun 1;61(11):4605-11 PMID: 11389097
Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.7400705
Email
[email protected]
Published
2006-06-00
Pages
599-604
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1479595
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.7400705 PMC Full Text View journal details
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