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Purification and characterization of endocan (endothelial cell‐specific molecule‐1), a circulating proteoglycan involved in tumour progression and inflammatory diseases
Author(s) -
Sarrazin Stéphane,
Bechard David,
Lassalle Philippe,
Lyon Malcolm,
Scherpereel Arnaud,
LortatJacob Hugues,
Ouatas Taoufik,
Delehedde Maryse
Publication year - 2004
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2004.390am.x
Subject(s) - hepatocyte growth factor , umbilical vein , chemokine , angiogenesis , proteoglycan , microbiology and biotechnology , proinflammatory cytokine , growth factor , inflammation , tumor necrosis factor alpha , chemistry , cancer research , biology , immunology , biochemistry , extracellular matrix , receptor , in vitro
By virtue of the multiplicity of their protein‐binding partners (e.g. growth factors, cytokines/chemokines), proteoglycans have been shown to be involved in the regulation of a large number of pathophysiological processes including cancer and inflammatory diseases. We have studied and characterized endocan, also called endothelial cell‐specific molecule‐1 (ESM‐1), which represents a new group of circulating proteoglycans. Endocan is mainly expressed by endothelial cells but also by epithelial cells from lung, gut and kidney. Structurally, endocan is constituted of a mature polypeptide of 165 amino acids with a single glycosaminoglycan chain covalently linked to the serine at position 137 (Béchard et al . 2001). Methods and results We showed that human umbilical vein endothelial cells expressed endocan specifically with a single chain of dermatan sulfate (DS) as glycosaminoglycan moiety. As shown by surface plasmon resonance, the DS chain directly interacts with cytokines and growth factors including hepatocyte growth factor/scatter factor and could be responsible for endocan's biological activities. Human embryonic kidney 293 cells, which have been genetically engineered to overexpress endocan, induce tumour growth when injected subcutaneously in SCID mice. Moreover, inflammatory cytokines such as TNF‐a and IL‐1 have been shown to increase the synthesis and the secretion of endocan from human umbilical vein endothelial cells. Conclusion These results suggest that circulating levels of endocan may represent a novel marker for cancer and inflammatory diseases. Further studies on its GAG structure could help us to better understand the biological activities of endocan and to design future glycomic‐based therapies.