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Inhibition of human HT-29 colon carcinoma cell adhesion by a 4-fluoro-glucosamine analogue

  • Glycoconjugate Journal
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Abstract

Cell surface glycoconjugates play an important role in cellular recognition and adhesion. Modification of these structures in tumour cells could affect tumour cell growth and behaviour, including metastasis. 2-Acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-α-D-glycopyranose (4-F-GlcNAc) was synthesized as a potential inhibitor and/or modifier of tumour cell glycoconjugates. The effect of this sugar analogue on the adhesive properties of human colon carcinoma HT-29 cells was evaluated. Treatment of HT-29 cells with 4-F-GlcNAc led to reduced cell surface expression of terminal lactosamine, sialyl-Lex and sialyl-Lea, as determined by Western blotting and flow cytometry. The aberrant expression of these oligosaccharide structures on the HT-29 cell surface resulted in: (1) decreased E-selectin mediated adhesion of human colon cells to human umbilical cord endothelial cells (HUVEC); (2) impaired adhesion of HT-29 cells to β-galactoside binding lectin, galectin-1; and (3) reduced ability to form homotypic aggregates. After exposure to 4-F-GlcNAc, lysosomal associated membrane proteins (lamp) 1 and 2, and carcinoembryonic antigen (CEA) detected in HT-29 cells were of lower molecular weight, probably due to impaired glycosylation. These results strongly suggest that modification of tumour cell surface molecules can alter tumour cell adhesion and that tumour cell surface oligosaccharides may be suitable targets for therapeutic exploitation.

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Abbreviations

4-F-GlcNAc:

2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-α-glucopyranose

GlcNAc:

N-acetylglucosamine

s-Lex :

sialyl-Lewisx

s-Lea :

sialyl-Lewisa

lamp-1 and lamp-2:

Lysosomal Associated Membrane Protein 1 and 2

CEA:

carcinoembryonic antigen

DMEM:

Dulbecco's Modified Eagle Medium

PBS:

Phosphate Buffered Saline (2.7 mM KCl, 1.5 mM KH2PO4, 137 mM NaCl, 6.5 mM Na2HPO4, pH 7.3)

BSA:

Bovine Serum Albumin

PMSF:

Phenylmethylsulfonylfluoride

TBS:

Tris Buffered Saline (10 mM Tris, 20 mM NaCl, pH 7.3)

TCA:

Trichloroacetic Acid

DSA:

Datura stramonium agglutinin

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Author notes

  1. Barbara Woynarowska

    Present address: Department of Radiology, University of Texas Health Science Center at San Antonio, 78284, San Antonio, TX, USA

Authors and Affiliations

  1. Department of Experimental Therapeutics, Roswell Park Cancer Institute, 14263, Buffalo, NY, USA

    Barbara Woynarowska, Charles J. Dimitroff, Moshewar Sharma & Ralph J. Bernacki

  2. Department of Gynecologic Oncology, Roswell Park Cancer Institute, 14263, Buffalo, NY, USA

    Khushi L. Matta

Authors
  1. Barbara Woynarowska
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  2. Charles J. Dimitroff
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  3. Moshewar Sharma
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  4. Khushi L. Matta
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  5. Ralph J. Bernacki
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Woynarowska, B., Dimitroff, C.J., Sharma, M. et al. Inhibition of human HT-29 colon carcinoma cell adhesion by a 4-fluoro-glucosamine analogue. Glycoconjugate J 13, 663–674 (1996). https://doi.org/10.1007/BF00731455

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  • DOI: https://doi.org/10.1007/BF00731455

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