Linked Life Data

14521590

Source:http://linkedlifedata.com/resource/pubmed/id/14521590

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-10-2
pubmed:abstractText
Most tumors have constitutively active tissue factor on their surface, capable of generating thrombin in the surrounding environment, and thrombosis is associated with cancer. Thrombin is known to induce a malignant phenotype by enhancing tissue adhesion and cell growth in vitro and in vivo in mice. Because tumors require angiogenesis for growth, we examined whether thrombin induces neoangiogenesis in a physiologically intact in vivo model. Thrombin (0.1 U mL-1) induced neoangiogenesis in the chick chorioallantoic membrane over a 24-72-h period by approximately 2-3-fold. This was inhibited by the potent thrombin inhibitor, hirudin and shown to have its mode of action by ligation of the thrombin protease-activated receptor, PAR-1. The thrombin receptor activation peptide, SFLLRNPNDKYEPF (200 microm) also enhanced neoangiogenesis c. 2-3-fold. Thrombin-induced neoangiogenesis was accompanied by the induction of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) mRNA at 24-48 h (approximately 2-fold) as determined by semi-quantitative reverse transcriptase-polymerase chain reaction. Thrombin-induced neoangiogenesis was inhibited to baseline level by the specific angiogenesis receptor inhibitors KDR-Fc (vs. VEGF) and Tie-2-Fc (vs. Ang-1 and Ang-2), as well as the non-specific angiogenesis inhibitor thrombospondin-1. Thrombin-induced neoangiogenesis was also inhibited to baseline level by agents known to inhibit thrombin receptor signaling in other cells: G-coupled protein receptor inhibitor, pertussis toxin (40 pg per egg), protein kinase C inhibitor, bisindolylmaleimide (1 microm per egg), MAP kinase inhibitor, PD980598 (10 microm per egg) and PI3 kinase inhibitor, LY294002 (0.25 microm per egg). Thus angiogenesis is stimulated by thrombosis, which could help explain the enhancement of experimental tumorigenesis by thrombin.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1538-7933
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2097-102
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14521590-Angiopoietin-2, pubmed-meshheading:14521590-Animals, pubmed-meshheading:14521590-Chick Embryo, pubmed-meshheading:14521590-Chorion, pubmed-meshheading:14521590-Dose-Response Relationship, Drug, pubmed-meshheading:14521590-Enzyme Inhibitors, pubmed-meshheading:14521590-Neovascularization, Pathologic, pubmed-meshheading:14521590-Peptides, pubmed-meshheading:14521590-Phenotype, pubmed-meshheading:14521590-RNA, Messenger, pubmed-meshheading:14521590-Receptor, PAR-1, pubmed-meshheading:14521590-Receptor, TIE-2, pubmed-meshheading:14521590-Recombinant Proteins, pubmed-meshheading:14521590-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14521590-Signal Transduction, pubmed-meshheading:14521590-Thrombin, pubmed-meshheading:14521590-Thrombospondin 1, pubmed-meshheading:14521590-Time Factors, pubmed-meshheading:14521590-Up-Regulation, pubmed-meshheading:14521590-Vascular Endothelial Growth Factor A, pubmed-meshheading:14521590-Vascular Endothelial Growth Factor Receptor-2
pubmed:year
2003
pubmed:articleTitle
Thrombin induces neoangiogenesis in the chick chorioallantoic membrane.
pubmed:affiliation
Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
pubmed:publicationType
Journal Article