Vascular PPARb/d Promotes Tumor Angiogenesis and Progression

PPARβ/δ has been suggested to be involved in the regulation of the angiogenic switch in tumor progression. However, until now it is not clear to what extent the expression of PPARβ/δ in tumor endothelium influences tumor progression and metastasis formation. We addressed this question using transgenic mice with an inducible conditional vascular-specific overexpression of PPARβ/δ. Following specific over-expression of PPARβ/δ in endothelial cells, we induced syngenic tumors. We observed an enhanced tumor growth, a higher vessel density, and enhanced metastasis formation in the tumors of animals with vessel-specific overexpression of PPARβ/δ. In order to identify molecular downstream targets of PPARβ/δ in the tumor endothelium, we sorted endothelial cells from the tumors and performed RNA sequencing.We show here that PPARβ/δ activation, regardless of its action on different cancer cell types, leads to a higher tumor vascularization which favors tumor growth and metastasis formation. Endothelial cells were isolated from tumors of Tie2-CreERT2;PPARβ/δ-flox+/− mice induced with Tamoxifen and the respective vehicle-treated controls, RNA was isolated from the endothelial cells and subjected to Ilumina mRNA HiSeq