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Epidemiology and Prevention |
INSERM U416, Institut Pasteur de Lille, 59019 Lille Cedex [A. S., T. G., B. G., S. S., A. T., A-B. T., P. L.]; Service de Pneumologie et dImmuno-Allergologie, Hôpital Albert Calmette, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille cedex [A. S., A-B. T.]; Laboratoire de Recherche de Pathologie, Université paris VII EA 2378 et INSERM ERIT-M, Hopital Saint Louis, 75 010 Paris, [A. J.]; Service dAnatomie Pathologique, Hôpital Brabois Adulte, 54511 Vandoeuvre Cedex [F. P.]; and Endotis Pharma, Parc Eurasanté, 59120 Loos [D. B.], France
Endocan is a proteoglycan specifically secreted by endothelial cells. Through its glycan domains, endocan binds to hepatocyte growth factor and increases its mitogenic activity. Here, we show that human embryonic kidney 293 cells, which have been genetically engineered to overexpress endocan, form tumors when injected s.c. in SCID mice. Both the glycan and a phenylalanine-rich region of endocan are necessary for mediating tumor growth activity. Blocking the phenylalanine-rich region with a monoclonal antibody results in a marked reduction of tumor growth. Finally, we report that circulating levels of endocan are increased in mice with the endocan-expressing human embryonic kidney 293 cell tumors and in a series of adult patients with lung cancer. Taken together, these results suggest that (a) endothelial-derived endocan induces tumor growth, (b) antibodies to endocan may have therapeutic potential, and (c) circulating levels of endocan may eventually represent a novel marker for cancer.
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