Antiangiogenic effects of latent antithrombin through perturbed cell-matrix interactions and apoptosis of endothelial cells.
Cancer Res
; 60(23): 6723-9, 2000 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-11118058
ABSTRACT
Antithrombin is a plasma protein of the serpin superfamily that may occur as several conformational variants. The native form of antithrombin is a major regulator of blood clotting. In the present study, we have identified the mechanism underlying the antiangiogenic action of a heat-denatured form, denoted latent antithrombin. Fibroblast growth factor (FGF)-induced angiogenesis in the chick embryo and angiogenesis in mouse fibrosarcoma tumors were inhibited by treatment with latent antithrombin at 1 mg/kg/day. Thermolysin-cleaved and native antithrombin were less efficient in these respects. Treatment with latent antithrombin induced apoptosis of cultured endothelial cells and inhibited cell migration toward FGF-2. Under these conditions, FGF-2-stimulated FGF receptor kinase activity was unaffected. However, actin reorganization, activation of focal adhesion kinase, and focal adhesion formation were disturbed by latent antithrombin treatment of FGF-2-stimulated endothelial cells. These data indicate that latent antithrombin induces apoptosis of endothelial cells by disrupting cell-matrix interactions through uncoupling of focal adhesion kinase.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Antitrombinas
/
Apoptose
/
Inibidores da Angiogênese
/
Fibrossarcoma
/
Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Suécia