Overexpression of endocan induces tumor formation

• Published in: Cancer research (Chicago, Ill.) Vol. 63; no. 18; pp. 6084 - 6089
• Main Authors: SCHERPEREEL, Arnaud, GENTINA, Thibaut, GRIGORIU, Bogdan, SENECHAL, Stéphanie, JANIN, Anne, TSICOPOULOS, Anne, PLENAT, Francois, BECHARD, David, TONNEL, André-Bernard, LASSALLE, Philippe
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.09.2003
• Subjects: Animals; Biological and medical sciences; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic - metabolism; DNA, Complementary - genetics; Fundamental and applied biological sciences. Psychology; HT29 Cells; Humans; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Lung Neoplasms - blood; Lung Neoplasms - pathology; Male; Mice; Mice, SCID; Molecular and cellular biology; Neoplasm Proteins; Phenylalanine - metabolism; Phenylalanine - physiology; Proteoglycans - biosynthesis; Proteoglycans - genetics; Proteoglycans - metabolism; Proteoglycans - physiology; Transfection; Human; Cell proliferation; Proteoglycan; Rodentia; Gene overexpression; Tumorigenicity; Malignant tumor; Gene expression; Carcinogenesis; Vertebrata; Mammalia; Mouse; Animal; Mechanism of action; Tumor cell
• ISSN: 0008-5472; 1538-7445

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.