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Biochim Biophys Acta. 2011 Dec;1810(12):1141-9. doi: 10.1016/j.bbagen.2011.09.011. Epub 2011 Sep 25.

Down-regulation of FUT3 and FUT5 by shRNA alters Lewis antigens expression and reduces the adhesion capacities of gastric cancer cells.

Author information

1
Programa de Recerca en Càncer, IMIM-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona, Spain.

Abstract

BACKGROUND:

Lewis antigens are fucosylated glycoconjugates involved in the development of several pathologies. The adhesion of sialyl-Lewis antigens to E-selectin is a key step in the development of metastasis and the glycosidic component of CD44 plays a key role in the binding to hyaluronic acid, a component of the extracellular matrix associated to tumor development and invasion. Fucosyltransferases are enzymes that add fucose to precursor glycan structures: FUT3 and FUT5 catalyze the addition of fucose to the α1-3,4 position and are detected in epithelial cells. In this study, we have analyzed the effects of silencing FUT3, FUT5 or FUT3/FUT5, in two gastric cancer cell lines, in the expression of Lewis antigens and in the adhesive and migratory capacities of the cells.

METHODS:

FUT3, FUT5 and FUT3/FUT5 were down-regulated using lentiviral delivery of shRNAs in MKN45 and GP220 gastric cancer cells.

RESULTS:

In the infected cells, decreased levels of FUT3 and FUT5 mRNA detected by quantitative RT-PCR; and lower levels of sialyl-Lewis antigens, evaluated by flow cytometry, were observed. The adhesion to endothelial cells trough the binding to E-selectin, and the binding to hyaluronic acid were reduced in the shFUT3, shFUT5 and shFUT3/FUT5, whereas the levels of CD44, analyzed by western blot, did not change.

GENERAL SIGNIFICANCE:

The down-regulation of FUT3, FUT5 and FUT3/FUT5 reduces the expression of sialyl-Lewis antigens and the adhesion and binding capacities of gastric cancer cells; and allows to identify the specific α1-3,4 fucosyltransferases implicated in the Lewis antigens synthesis in this cellular model.

PMID:
21978830
DOI:
10.1016/j.bbagen.2011.09.011
[Indexed for MEDLINE]

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