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 γ (PPARγ), 15-deoxy-Δ12,14-prostaglandin J2, troglitazone, and rosiglitazone increased PPARγ and CD36 expression in endothelial cells and improved the efficacy of TSP1 and ABT510 in a CD36-dependent manner. The ABT510 and PPARγ ligands cooperatively blocked angiogenic endothelial functions in vitro and neovascularization in vivo. In tumor xenografts, 15-deoxy-Δ12,14-prostaglandin J2 and troglitazone synergistically improved antiangiogenic and antitumor effects of ABT510. Our data provide one mechanism for the in vivo angioinhibitory effect of PPARγ ligands and show fine-tuning of the antiangiogenic efficacy via targeted up-regulation of the endothelial receptor.
|Original language||English (US)|
|Number of pages||10|
|Journal||Molecular Cancer Research|
|State||Published - Oct 2004|
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research