Glycobiology, 2001, Vol. 11, No. 7 587-592
© 2001 Oxford University Press
Cell surface–expressed Thomsen-Friedenreich antigen in colon cancer is predominantly carried on high molecular weight splice variants of CD44
2Department of Medicine, University of Liverpool, Daulby Street, Liverpool L69 3GA, UK, 3School of Biological Sciences, University of Liverpool, Daulby Street, Liverpool L69 3BX, UK, 4Imperial Cancer Research Fund, Histopathology Unit, 35-43 Lincoln’s Inn Fields, London WC2A 3PN, UK, and 5Imperial College School of Science Medicine and Technology, Hammersmith Campus, Ducane Road, London W12 ONN, UK
Increased mucosal expression of TF, the Thomsen-Friedenreich oncofetal blood group antigen (galactose ß1-3 N-acetylgalactosamine 
-) occurs in colon cancer and colitis. This allows binding of TF-specific lectins, such as peanut agglutinin (PNA), which is mitogenic to the colorectal epithelium. To identify the cell surface TF-expressing glycoprotein(s), HT29 and Caco2 colon cancer cells were surface-labeled with Na[125I] and subjected to PNA-agarose affinity purification and electrophoresis. Proteins, 
110–180 kDa, present in HT29 but not Caco2 were identified by Western blotting as high molecular weight splice variants of CD44 (CD44v). Selective removal of TF antigen by Streptococcus pneumoniae endo--N-acetylgalactosaminidase substantially reduced PNA binding to CD44v. Immunoprecipitated CD44v from HT29 cell extracts also expressed sialyl-Tn (sialyl 2-6 N-acetylgalactosamine-). Incubation of PNA 15 µg/ml with HT29 cells caused no additional proliferative effect in the presence of anti-CD44v6 mAb. In colon cancer tissue extracts (N = 3) PNA bound to CD44v but not to standard CD44. These data show that CD44v is a major PNA-binding glycoprotein in colon cancer cells. Because CD44 high molecular weight splice variants are present in colon cancer and inflammatory bowel disease tissue but are absent from normal mucosa, these results may also explain the increased PNA reactivity in colon cancer and inflammatory bowel disease. The coexpression of oncofetal carbohydrate antigens TF and sialyl-Tn on CD44 splice variants provides a link between cancer-associated changes in glycosylation and CD44 splicing, both of which correlate with increased metastatic potential.
1 To whom correspondence should be addressed
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Q. Zhao, X. Guo, G. B. Nash, P. C. Stone, J. Hilkens, J. M. Rhodes, and L.-G. Yu Circulating Galectin-3 Promotes Metastasis by Modifying MUC1 Localization on Cancer Cell Surface Cancer Res., September 1, 2009; 69(17): 6799 - 6806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Singh, S. Subramanian, J. M. Rhodes, and B. J. Campbell Peanut lectin stimulates proliferation of colon cancer cells by interaction with glycosylated CD44v6 isoforms and consequential activation of c-Met and MAPK: functional implications for disease-associated glycosylation changes Glycobiology, July 1, 2006; 16(7): 594 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Julien, E. Adriaenssens, K. Ottenberg, A. Furlan, G. Courtand, A.-S. Vercoutter-Edouart, F.-G. Hanisch, P. Delannoy, and X. Le Bourhis ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity Glycobiology, January 1, 2006; 16(1): 54 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Abstracts Gut, April 1, 2004; 53(suppl_3): a1 - a123. [Full Text] [PDF]
|
|
|
|
|
|
V. V. Glinsky, G. V. Glinsky, O. V. Glinskii, V. H. Huxley, J. R. Turk, V. V. Mossine, S. L. Deutscher, K. J. Pienta, and T. P. Quinn Intravascular Metastatic Cancer Cell Homotypic Aggregation at the Sites of Primary Attachment to the Endothelium Cancer Res., July 1, 2003; 63(13): 3805 - 3811. [Abstract] [Full Text] [PDF]
|
|