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J. Biol. Chem., Vol. 276, Issue 51, 48341-48349, December 21, 2001
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From Proteoglycans that modulate the activities of
growth factors, chemokines, and coagulation factors regulate in turn
the vascular endothelium with respect to processes such as
inflammation, hemostasis, and angiogenesis. Endothelial cell-specific
molecule-1 is mainly expressed by endothelial cells and regulated by
pro-inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden,
J. V., Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271, 20458-20464). We
demonstrate that this molecule is secreted as a soluble dermatan
sulfate (DS) proteoglycan. This proteoglycan represents the
major form either secreted by cell lines or circulating in the human
bloodstream. Because this proteoglycan is specifically secreted by
endothelial cells, we propose to name it endocan. The glycosaminoglycan
component of endocan consists of a single DS chain covalently attached
to serine 137. Endocan dose-dependently increased the
hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation
of human embryonic kidney cells, whereas the nonglycanated form of
endocan did not. Moreover, DS chains purified from endocan mimicked the
endocan-mediated increase of cell proliferation in the presence of
HGF/SF. Overall, our results demonstrate that endocan is a novel
soluble dermatan sulfate proteoglycan produced by endothelial cells.
Endocan regulates HGF/SF-mediated mitogenic activity and may support
the function of HGF/SF not only in embryogenesis and tissue repair
after injury but also in tumor progression.
Endocan Is a Novel Chondroitin Sulfate/Dermatan Sulfate
Proteoglycan That Promotes Hepatocyte Growth Factor/Scatter Factor
Mitogenic Activity*
,,,
,,,, and
INSERM U416, Institut Pasteur de Lille, 1 Rue du
Dr. A Calmette, 59019 Lille, France, § School of
Biological Sciences, University of Liverpool,
L69 7ZB Liverpool, United Kingdom, ¶ Cancer Research Campaign
Department of Medical Oncology, University of Manchester, Christie
Hospital NHS Trust, Wilmslow Road,
Manchester M20 4BX, United Kingdom, CNRS UMR 8526, Institut
de Biologie de Lille, 1 Rue du Dr. A Calmette,
§§ Laboratoire d'Hématologie A, Hopital
Cardiologique, CHRU, Boulevard du Pr. Jules Leclercq,
59019 Lille, France, ** ICOS Corporation,
Bothell, Washington 98021, INSERM U377, 1 Place de Verdun, 59019 Lille, and ¶¶ Service
d'Anatomie Pathologique, Hopital Saint-Louis, 1 Avenue C. Vellefaux,
75475 Paris, France
*
This work was supported by PROGRES Research Program from
INSERM, the Societé d'Enseignement et de Recherche en
Pneumologie et Allergie, the Cancer and Polio Research Fund, the Cancer
Research Campaign, and the Northwest Cancer Research Fund.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: INSERM
U416, Institut Pasteur de Lille, 1 Rue du Pr A Calmette, B.P 245, 59019 Lille Cedex, France. Tel.: 33 3 20 87 78 80; Fax: 33 3 20 87 73 45;
E-mail: philippe.lassalle@pasteur-lille.fr.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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