The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease

Nicole C. Smits, Sindhulakshmi Kurup, Angelique L. Rops, Gerdy B. Ten Dam, Leon F. Massuger, Theo Hafmans, Jeremy E. Turnbull, Dorothe Spillmann, Jin Ping Li, Stephen Kennel, Jonathan Wall, Nicholas W. Shworak, P. N.Richard Dekhuijzen, Johan Van Der Vlag, Toin H. Van Kuppevelt

Research output: Contribution to journalArticle

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Abstract

Heparan sulfate (HS) is a structurally complex polysaccharide that interacts with a broad spectrum of extracellular effector ligands and thereby is thought to regulate a diverse array of biologic processes. The specificity of HS-ligand interactions is determined by the arrangement of sulfate groups on HS, which creates distinct binding motifs. Biologically important HS motifs are expected to exhibit regulated expression, yet there is a profound lack of tools to identify such motifs; consequently, little is known of their structures and functions. We have identified a novel phage display-derived antibody (NS4F5) that recognizes a highly regulated HS motif (HSNS4F5), which we have rigorously identified as (GlcNS6S-IdoA2S)3. HSNS4F5 exhibits a restricted expression in healthy adult tissues. Blocking HSNS4F5 on cells in culture resulted in reduced proliferation and enhanced sensitivity to apoptosis. HSNS4F5 is up-regulated in tumor endothelial cells, consistent with a role in endothelial cell activation. Indeed, TNF-α stimulated endothelial expression of HSNS4F5, which contributed to leukocyte adhesion. In a mouse model of severe systemic amyloid protein A amyloidosis, HSNS4F5 was expressed within amyloid deposits, which were successfully detected by microSPECT imaging using NS4F5 as a molecularly targeted probe. Combined, our results demonstrate that NS4F5 is a powerful tool for elucidating the biological function of HSNS4F5 and can be exploited as a probe to detect novel polysaccharide biomarkers of disease processes.

Original languageEnglish (US)
Pages (from-to)41143-41151
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number52
DOIs
StatePublished - Dec 24 2010

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Heparitin Sulfate
Topography
Heparin
Endothelial cells
Polysaccharides
Endothelial Cells
Ligands
Serum Amyloid A Protein
Bacteriophages
Amyloid Plaques
Biomarkers
Amyloidosis
Amyloid
Sulfates
Tumors
Leukocytes
Adhesion
Deposits
Cell Culture Techniques
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Smits, N. C., Kurup, S., Rops, A. L., Ten Dam, G. B., Massuger, L. F., Hafmans, T., ... Van Kuppevelt, T. H. (2010). The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease. Journal of Biological Chemistry, 285(52), 41143-41151. https://doi.org/10.1074/jbc.M110.153791

The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease. / Smits, Nicole C.; Kurup, Sindhulakshmi; Rops, Angelique L.; Ten Dam, Gerdy B.; Massuger, Leon F.; Hafmans, Theo; Turnbull, Jeremy E.; Spillmann, Dorothe; Li, Jin Ping; Kennel, Stephen; Wall, Jonathan; Shworak, Nicholas W.; Dekhuijzen, P. N.Richard; Van Der Vlag, Johan; Van Kuppevelt, Toin H.

In: Journal of Biological Chemistry, Vol. 285, No. 52, 24.12.2010, p. 41143-41151.

Research output: Contribution to journalArticle

Smits, NC, Kurup, S, Rops, AL, Ten Dam, GB, Massuger, LF, Hafmans, T, Turnbull, JE, Spillmann, D, Li, JP, Kennel, S, Wall, J, Shworak, NW, Dekhuijzen, PNR, Van Der Vlag, J & Van Kuppevelt, TH 2010, 'The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease', Journal of Biological Chemistry, vol. 285, no. 52, pp. 41143-41151. https://doi.org/10.1074/jbc.M110.153791
Smits, Nicole C. ; Kurup, Sindhulakshmi ; Rops, Angelique L. ; Ten Dam, Gerdy B. ; Massuger, Leon F. ; Hafmans, Theo ; Turnbull, Jeremy E. ; Spillmann, Dorothe ; Li, Jin Ping ; Kennel, Stephen ; Wall, Jonathan ; Shworak, Nicholas W. ; Dekhuijzen, P. N.Richard ; Van Der Vlag, Johan ; Van Kuppevelt, Toin H. / The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 52. pp. 41143-41151.
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