Unknown

Dataset Information

0

Alternatively spliced tissue factor induces angiogenesis through integrin ligation.


ABSTRACT: The initiator of coagulation, full-length tissue factor (flTF), in complex with factor VIIa, influences angiogenesis through PAR-2. Recently, an alternatively spliced variant of TF (asTF) was discovered, in which part of the TF extracellular domain, the transmembrane, and cytoplasmic domains are replaced by a unique C terminus. Subcutaneous tumors produced by asTF-secreting cells revealed increased angiogenesis, but it remained unclear if and how angiogenesis is regulated by asTF. Here, we show that asTF enhances angiogenesis in matrigel plugs in mice, whereas a soluble form of flTF only modestly enhances angiogenesis. asTF dose-dependently upregulates angiogenesis ex vivo independent of either PAR-2 or VIIa. Rather, asTF was found to ligate integrins, resulting in downstream signaling. asTF-alphaVbeta3 integrin interaction induces endothelial cell migration, whereas asTF-dependent formation of capillaries in vitro is dependent on alpha6beta1 integrin. Finally, asTF-dependent aortic sprouting is sensitive to beta1 and beta3 integrin blockade and a TF-antibody that disrupts asTF-integrin interaction. We conclude that asTF, unlike flTF, does not affect angiogenesis via PAR-dependent pathways but relies on integrin ligation. These findings indicate that asTF may serve as a target to prevent pathological angiogenesis.

SUBMITTER: van den Berg YW 

PROVIDER: S-EPMC2780792 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Alternatively spliced tissue factor induces angiogenesis through integrin ligation.

van den Berg Y W YW   van den Hengel L G LG   Myers H R HR   Ayachi O O   Jordanova E E   Jordanova E E   Ruf W W   Spek C A CA   Reitsma P H PH   Bogdanov V Y VY   Versteeg H H HH  

Proceedings of the National Academy of Sciences of the United States of America 20091029 46


The initiator of coagulation, full-length tissue factor (flTF), in complex with factor VIIa, influences angiogenesis through PAR-2. Recently, an alternatively spliced variant of TF (asTF) was discovered, in which part of the TF extracellular domain, the transmembrane, and cytoplasmic domains are replaced by a unique C terminus. Subcutaneous tumors produced by asTF-secreting cells revealed increased angiogenesis, but it remained unclear if and how angiogenesis is regulated by asTF. Here, we show  ...[more]

Similar Datasets

| S-EPMC4190117 | biostudies-literature
| S-EPMC3710867 | biostudies-literature
| S-EPMC2839007 | biostudies-literature
| S-EPMC3409277 | biostudies-literature
| S-EPMC4039448 | biostudies-literature
| S-EPMC3994711 | biostudies-literature
| S-EPMC8471299 | biostudies-literature
| S-EPMC5739307 | biostudies-literature
| S-EPMC4560996 | biostudies-literature
| S-EPMC4122306 | biostudies-literature