Abstract
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members—PPARα, PPARδ, and PPARγ—that differ in their cell and tissue distribution as well as in their target genes. PPARα is abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPARα, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we focus on the contribution of PPARα to tumor and endothelial cell functions and provide compelling evidence that PPARα can be viewed as a new class of ligand activated tumor “suppressor” gene with antiangiogenic and antitumorigenic activities. Given that PPAR ligands are currently used in medicine as hypolipidemic drugs with excellent tolerance and limited toxicity, PPARα activation might offer a novel and potentially low-toxic approach for the treatment of tumor-associated angiogenesis and cancer.
Highlights
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors
The observation that members of the PPAR family are expressed by tumor and endothelial cells [13, 14] together with the finding that PPAR ligands regulate cell growth, survival, migration, and invasion [15, 16] prompted investigators to determine whether these receptors play a role in the pathophysiology of tumorigenesis and angiogenesis [17, 18]
The studies summarized in this review identify PPARα as a potential host-based target for the development of new antiangiogenic approaches to inhibit and/or prevent tumor growth
Summary
The observation that members of the PPAR family are expressed by tumor and endothelial cells [13, 14] together with the finding that PPAR ligands regulate cell growth, survival, migration, and invasion [15, 16] prompted investigators to determine whether these receptors play a role in the pathophysiology of tumorigenesis and angiogenesis [17, 18]. The anticancer effects of PPARγ agonists have been extensively studied because of their antiproliferative, proapoptotic, antiapoptotic, and differentiation-promoting activities [19]. In this context, activation of PPARγ has been. Disruption of the PPARγ gene in the intestine enhances tumorigenesis in ApcMin /+ mice [28] These studies suggest that PPARγ functions as a tumor suppressor factor and its activation might be beneficial for patients with tumors, PPARγ agonists have been shown to increase the frequency of colon tumors [29] and to promote edema [30]. We highlight some of the key functions attributed to PPARα in the context of endothelial and tumor cell biology
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