Peroxisome proliferator-activated receptor gamma ligands improve the antitumor efficacy of thrombospondin peptide ABT510.
Mol Cancer Res
; 2(10): 541-50, 2004 Oct.
Article
en En
| MEDLINE
| ID: mdl-15498928
ABSTRACT
An expanding capillary network is critical for several pathologic conditions. In cancer, the decrease of antiangiogenic thrombospondin-1 (TSP1) often enables an angiogenic switch, which can be reversed with exogenous TSP1 or its peptide derivative ABT510. TSP1 acts by inducing endothelial cell apoptosis via signaling cascade initiated at CD36, a TSP1 antiangiogenic receptor. Here, we show that the ligands of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), 15-deoxy-delta(12,14)-prostaglandin J2, troglitazone, and rosiglitazone increased PPARgamma and CD36 expression in endothelial cells and improved the efficacy of TSP1 and ABT510 in a CD36-dependent manner. The ABT510 and PPARgamma ligands cooperatively blocked angiogenic endothelial functions in vitro and neovascularization in vivo. In tumor xenografts, 15-deoxy-delta(12,14)-prostaglandin J2 and troglitazone synergistically improved antiangiogenic and antitumor effects of ABT510. Our data provide one mechanism for the in vivo angioinhibitory effect of PPARgamma ligands and show fine-tuning of the antiangiogenic efficacy via targeted up-regulation of the endothelial receptor.
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Bases de datos:
MEDLINE
Asunto principal:
Prostaglandina D2
/
Trombospondina 1
/
Inhibidores de la Angiogénesis
/
PPAR gamma
/
Neovascularización Patológica
Límite:
Humans
Idioma:
En
Revista:
Mol Cancer Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos