Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber. Effect on Tumor Metastasis and Neutrophil Recruitment.
From: Zurich Center for Integrative Human Physiology and Institute of Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
The Journal of biological chemistry
- Publish Date: May 2007
- ISSN: 0021-9258
- Volume: 282
- Issue: 20
- Pages: 14984-91
- Medium: Print
- Language: English
- Citation (JAMA): Borsig Lubor, Wang Lianchun, Cavalcante Moises C M, et al. Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber. Effect on Tumor Metastasis and Neutrophil Recruitment.. J. Biol. Chem. May 2007;282:14984-91
Abstract
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.
Mesh Headings (Keywords): Adenocarcinoma, Animals, Anticoagulants, Carbohydrate Conformation, Cell Adhesion, Chondroitin Sulfates, Disease Models, Animal, Dose-Response Relationship, Drug, Heparin, L-Selectin, Lipopolysaccharides, Lung Neoplasms, Mice, Neoplasm Metastasis, Neoplasms, Experimental, Neutrophil Infiltration, P-Selectin, Partial Thromboplastin Time, Peritonitis, Pneumonia, Sea Cucumbers, Thioglycolates
Check for Full Text / PubMed Unique Identifier (PMID): 17371880
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.