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Cited by 187Proteoglycans and glycosaminoglycans researchCell Adhesion Molecules ResearchGlycosylation and Glycoproteins Research

Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber

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Borsig, Lubor, Wang, Lianchun, Cavalcante, Moises C.M., Cardilo-Reis, Larissa, Ferreira, Paola L., Mourąo, Paulo A.S., Esko, Jeffrey D., Pavąo, Mauro S.G.·2007·Journal of Biological Chemistry
DOI 10.1074/jbc.m610560200
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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.

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  • Some polysaccharides from marine animals inhibited the binding of pro-inflammatory molecules P- and L-selectins to immobilized carbohydrate determinant sialyl Lewisx.

    “Some polysaccharides from the marine animals inhibited the binding of pro-inflammatory molecules, P- and L-selectins, to immobilized carbohydrate determinant sialyl Lewisx which is a component of cell surface glycoproteins presented in leukocytes and overexpressed in several tumor cells.”

    From Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects (2013) · cites this paper as [150]

  • As a consequence of their antiselectin activity, these polysaccharides attenuated metastasis and inflammation.

    “As a consequence of their antiselectin activity, these polysaccharides attenuated metastasis and inflammation [150,151,152].”

    From Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects (2013) · cites this paper as [150]

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Authors
Borsig, L., Wang, L., Cavalcante, M. C. M., Cardilo-Reis, L., Ferreira, P. L., Mourąo, P. A. S., Esko, J. D., & Pavąo, M. S. G.
Affiliations
  • University of Zurich (CH)
  • University of Georgia (US)
  • Universidade Federal do Rio de Janeiro (BR)
  • University of California San Diego (US)
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2007-05
Volume
282
Issue
20
Pages
14984-14991
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m610560200
OpenAlex
W2014449340
Cited by
187
References
51
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 17 · 2019: 17 · 2018: 11 · 2017: 16 · 2016: 11 · 2015: 16 · 2014: 18 · 2013: 8 · 2012: 6
FWCI
2.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (100303, 3100A0)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
  • Universidade Federal do Rio de Janeiro
  • National Institutes of Health (HL57345)
  • National Heart, Lung, and Blood Institute (HL 57345, P01HL057345)
  • National Cancer Institute (CA11227)
  • Fogarty International Center (R03 TW05775, R03TW005775)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
fucosylated chondroitin sulfate, sea cucumber polysaccharides, P-selectin, L-selectin, sialyl Lewis X, heparin alternatives, experimental metastasis, lung colonization, neutrophil recruitment, inflammation, glycosaminoglycans
MeSH terms
Adenocarcinoma, Animals, Anticoagulants, Carbohydrate Conformation, Cell Adhesion, Chondroitin Sulfates, Disease Models, Animal, Dose-Response Relationship, Drug, Heparin, Lipopolysaccharides, Lung Neoplasms, Neoplasm Metastasis, Neoplasms, Experimental, Partial Thromboplastin Time, Peritonitis, Pneumonia, Sea Cucumbers, Thioglycolates, P-Selectin, L-Selectin, Neutrophil Infiltration, Mice

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