Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2007-5-14
pubmed:abstractText
Heparin is an excellent inhibitor of P- and L-selectin binding to the carbohydrate determinant, sialyl Lewis(x). As a consequence of its anti-selectin activity, heparin attenuates metastasis and inflammation. Here we show that fucosylated chondroitin sulfate (FucCS), a polysaccharide isolated from sea cucumber composed of a chondroitin sulfate backbone substituted at the 3-position of the beta-D-glucuronic acid residues with 2,4-disulfated alpha-L-fucopyranosyl branches, is a potent inhibitor of P- and L-selectin binding to immobilized sialyl Lewis(x) and LS180 carcinoma cell attachment to immobilized P- and L-selectins. Inhibition occurs in a concentration-dependent manner. Furthermore, FucCS was 4-8-fold more potent than heparin in the inhibition of the P- and L-selectin-sialyl Lewis(x) interactions. No inhibition of E-selectin was observed. FucCS also inhibited lung colonization by adenocarcinoma MC-38 cells in an experimental metastasis model in mice, as well as neutrophil recruitment in two models of inflammation (thioglycollate-induced peritonitis and lipopolysaccharide-induced lung inflammation). Inhibition occurred at a dose that produces no significant change in plasma activated partial thromboplastin time. Removal of the sulfated fucose branches on the FucCS abolished the inhibitory effect in vitro and in vivo. Overall, the results suggest that invertebrate FucCS may be a potential alternative to heparin for blocking metastasis and inflammatory reactions without the undesirable side effects of anticoagulant heparin.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14984-91
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17371880-Adenocarcinoma, pubmed-meshheading:17371880-Animals, pubmed-meshheading:17371880-Anticoagulants, pubmed-meshheading:17371880-Carbohydrate Conformation, pubmed-meshheading:17371880-Cell Adhesion, pubmed-meshheading:17371880-Chondroitin Sulfates, pubmed-meshheading:17371880-Disease Models, Animal, pubmed-meshheading:17371880-Dose-Response Relationship, Drug, pubmed-meshheading:17371880-Heparin, pubmed-meshheading:17371880-L-Selectin, pubmed-meshheading:17371880-Lipopolysaccharides, pubmed-meshheading:17371880-Lung Neoplasms, pubmed-meshheading:17371880-Mice, pubmed-meshheading:17371880-Neoplasm Metastasis, pubmed-meshheading:17371880-Neoplasms, Experimental, pubmed-meshheading:17371880-Neutrophil Infiltration, pubmed-meshheading:17371880-P-Selectin, pubmed-meshheading:17371880-Partial Thromboplastin Time, pubmed-meshheading:17371880-Peritonitis, pubmed-meshheading:17371880-Pneumonia, pubmed-meshheading:17371880-Sea Cucumbers, pubmed-meshheading:17371880-Thioglycolates
pubmed:year
2007
pubmed:articleTitle
Selectin blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea cucumber. Effect on tumor metastasis and neutrophil recruitment.
pubmed:affiliation
Zurich Center for Integrative Human Physiology and Institute of Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural