Overexpression of endocan induces tumor formation.
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.
Scherpereel
Arnaud
A
INSERM U416, Institut Pasteur de Lille, France.
Gentina
Thibaut
T
Grigoriu
Bogdan
B
Sénéchal
Stéphanie
S
Janin
Anne
A
Tsicopoulos
Anne
A
Plénat
François
F
Béchard
David
D
Tonnel
André-Bernard
AB
Lassalle
Philippe
P
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins; D010649:Phenylalanine / Q000378:metabolism / Q000502:physiology; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D018076:DNA, Complementary; C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D010649:Phenylalanine