Transgene Expression of α(1,2)-Fucosyltransferase-I (FUT1) in Tumor Cells Selectively Inhibits Sialyl-Lewis x Expression and Binding to E-Selectin without Affecting Synthesis of Sialyl-Lewis a or Binding to P-Selectin
| Autor: | Sylvie Mathieu, Pierre Bongrand, Claire Langlet, Maëlle Prorok, Assou El-Battari, Rathviro Uch, René Gerolami, Anne-Marie Benoliel |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CA-19-9 Antigen
Short Communication Genetic Vectors Immunoblotting Oligosaccharides Transfection Fluorescence Pathology and Forensic Medicine HT29 Cells chemistry.chemical_compound Transduction Genetic Gangliosides E-selectin Cell Adhesion Animals Humans Transgenes Sialyl Lewis X Antigen Cell adhesion Membrane Glycoproteins biology Endothelial Cells Sialyl-Lewis A Flow Cytometry Fucosyltransferases Molecular biology P-Selectin Sialyl-Lewis X chemistry Cancer cell HIV-1 biology.protein E-Selectin Selectin |
| Zdroj: | The American Journal of Pathology. 164:371-383 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)63127-6 |
| Popis: | During inflammation, E- and P-selectins appear on activated endothelial cells to interact with leukocytes through sialyl-Lewis x and sialyl-Lewis a antigens (sLe(x/a)). These selectins can also interact with tumor cells in a sialyl-Lewis-dependent manner and for this reason, they are thought to play a key role in metastasis. Diverting the biosynthesis of sialyl-Lewis antigens toward nonadhesive structures is an attractive gene therapy for preventing the hematogenous metastatic spread of cancers. We have previously shown that transfection of alpha(1,2)-fucosyltransferase-I (FUT1) in Chinese hamster ovary (CHO) cells had a slight effect on the overall sialylation while the synthesis of sLE(x) was dramatically prevented. We herein delivered the gene of FUT1 by a human immunodeficiency virus-derived lentiviral vector to three human cancer cell lines including pancreatic (BxPC3), hepatic (HepG2), and colonic (HT-29) cancer cells. We found that on FUT1 transduction, all cells exhibited a dramatic decrease in sLe(x) synthesis with a concomitant increase in Le(y) and Le(b) expression, without any detectable effect on the level of cell surface sLe(a) antigens. In parallel, FUT1-transduced HT-29 and HepG2 cells, but not BxPC3 cells, failed to interact with E-selectin as assessed by E-selectin-binding assay or dynamic adhesion to activated endothelial cells. We show also that transduced FUT1 efficiently fucosylates the P-selectin ligand PSGL-1 without altering P-selectin binding. These results have important implications for understanding cell-specific reactions underlying the synthesis of selectin ligands in cancer cells and may provide a basis for the development of anti-metastatic gene therapy. |
| Databáze: | OpenAIRE |
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