Linked Life Data

12782582

Source:http://linkedlifedata.com/resource/pubmed/id/12782582

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-6-3
pubmed:abstractText
Clustered presentation of sialyl Lewis X (sLe(X)) on tumor cell mucins is thought to facilitate metastasis through binding to selectin adhesion receptors expressed on platelets, leukocytes and endothelial cells. Thus, interfering with sLe(X) assembly might provide a chemotherapeutic method for treating metastatic disease. Prior studies have shown that peracetylated disaccharides can act in cells as substrates for the assembly of oligosaccharides related to sLe(X) synthesis, and the assembly of oligosaccharides on the disaccharides diverts the assembly of sLe(X) from endogenous cell surface glycoconjugates. Here, we show that treatment of cultured human adenocarcinoma cells with micromolar concentrations of the peracetylated disaccharide, (Ac)(6)GlcNAcbeta1,3Galbeta-O-naphthalenemethanol (AcGnG-NM) reduces the expression of sLe(X) and diminishes binding in vitro to selectin-coated dishes, thrombin-activated platelets, and tumor necrosis factor alpha-activated endothelial cells. Altering glycosylation in this way significantly reduced the ability of tumor cells to distribute to the lungs of wild-type mice over a 3-h period after i.v. injection. No significant difference in biodistribution was noted after the injection of AcGnG-NM-treated tumor cells into P-selectin deficient mice, although the extent of lung seeding was reduced compared with that in wild-type mice. In vitro, we demonstrate that normal mouse platelets, but not P-selectin-deficient platelets, bound to control tumor cells and protected them from leukocyte-mediated cytolysis. Conversely, treatment of tumor cells with disaccharide markedly reduced the ability of normal platelets to protect them from cytolysis. Finally, in an experimental metastasis model, we show that treatment of tumor cells with the disaccharide markedly reduced their lung colonization potential after injection into severe combined immunodeficient mice. These findings suggest that this compound may represent a novel class of chemotherapeutic agents for prevention and treatment of metastatic disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2775-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
A disaccharide precursor of sialyl Lewis X inhibits metastatic potential of tumor cells.
pubmed:affiliation
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Diego, California, 92103-0687, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't