A receptor for vascular endothelial growth factor that stimulates endothelial apoptosis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2001-12, Vol.61 (24), p.8629-8637
• Main Authors: QUINN, Timothy P, SOIFER, Scott J, RAMER, Kevin, WILLIAMS, Lewis T, NAKAMURA, Mary C
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Aorta - cytology; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Cell Line; Chemotherapy; Chimerin Proteins - genetics; Chimerin Proteins - metabolism; Chimerin Proteins - physiology; Dimerization; DNA, Complementary - genetics; Endothelial Growth Factors - metabolism; Endothelial Growth Factors - pharmacology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; fas Receptor - genetics; fas Receptor - metabolism; fas Receptor - physiology; Humans; Lymphokines - metabolism; Lymphokines - pharmacology; Medical sciences; Pharmacology. Drug treatments; Protein Structure, Tertiary; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases - physiology; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Receptors, Growth Factor - physiology; Receptors, Vascular Endothelial Growth Factor; Swine; Transfection; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0008-5472; 1538-7445

Vascular endothelial growth factor (VEGF) is a dimeric angiogenic factor that is overexpressed by many tumors and stimulates tumor angiogenesis. VEGF initiates signaling by dimerizing the receptors VEGFR-1 and VEGFR-2. The Fas receptor stimulates apoptosis, and artificial dimerization of the Fas cytoplasmic domain has been shown to induce apoptosis. We constructed a chimeric receptor (VEGFR2Fas) combining the extracellular and transmembrane domains of VEGFR-2 with the cytoplasmic domain of Fas receptor. When VEGFR2Fas was stably expressed in endothelial cells in vitro, treatment with VEGF rapidly induced cell death with features characteristic of Fas-mediated apoptosis. These findings demonstrate that VEGFR2Fas functions as a VEGF-triggered death receptor and raise the possibility that introduction of VEGFR2Fas into tumor endothelium or tumor cells in vivo may convert tumor-derived VEGF from an angiogenic factor into an antiangiogenesis agent.