15( S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires STAT3-dependent expression of VEGF

15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE] activated signal transducer and activator of transcription 3 (STAT3) as measured by its tyrosine phosphorylation, translocation from the cytoplasm to the nucleus, DNA binding, and reporter gene activity in human dermal microvascular endothelial cells (...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2007-05, Vol.67 (9), p.4328-4336
Main Authors: SRIVASTAVA, Kalyan, KUNDUMANI-SRIDHARAN, Venkatesh, BAOLIN ZHANG, BAJPAI, Arun K, RAO, Gadiparthi N
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Aorta - drug effects
Biological and medical sciences
Cell Movement - physiology
Collagen
Drug Combinations
Endothelial Cells - cytology
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Humans
Hydroxyeicosatetraenoic Acids - pharmacology
In Vitro Techniques
Laminin
Male
Medical sciences
Mice
Mice, Inbred C57BL
Neovascularization, Physiologic - drug effects
Neovascularization, Physiologic - physiology
Pharmacology. Drug treatments
Proteoglycans
Rats
Rats, Inbred F344
STAT3 Transcription Factor - metabolism
Tumors
Vascular Endothelial Growth Factor A - biosynthesis
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Summary:15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE] activated signal transducer and activator of transcription 3 (STAT3) as measured by its tyrosine phosphorylation, translocation from the cytoplasm to the nucleus, DNA binding, and reporter gene activity in human dermal microvascular endothelial cells (HDMVEC). Inhibition of STAT3 activation via adenovirus-mediated expression of its dominant-negative mutant suppressed 15(S)-HETE-induced HDMVEC migration and tube formation in vitro and aortic ring and Matrigel plug angiogenesis in vivo. 15(S)-HETE induced the expression of vascular endothelial growth factor (VEGF) in a time- and STAT3-dependent manner in HDMVEC. In addition, neutralizing anti-VEGF antibodies blocked 15(S)-HETE-induced HDMVEC migration and tube formation in vitro and aortic ring and Matrigel plug angiogenesis in vivo. Together, these results show for the first time that 15(S)-HETE-induced angiogenesis requires STAT3-dependent expression of VEGF. In view of these findings, it is suggested that eicosanoids, particularly 15(S)-HETE, via its capacity to stimulate angiogenesis, may influence the progression of cancer and vascular disease.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-06-3594