Anti- and Protumorigenic Effects of PPARγ in Lung Cancer Progression: A Double-Edged Sword

Figure 2

The role of PPARγ signaling in the tumor microenvironment. Activation of PPARγ in macrophages promotes a tumor-associated phenotype, which leads to increased tumor angiogenesis, matrix breakdown, and tumor cell motility. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis in mice. Similarly, activation of PPARγ in the tumor microenvironment leads to generation of Tregs and inhibition of host T-cell antitumor activity, resulting in an immunosuppressive environment that promotes tumor progression. TZDs have been shown to inhibit angiogenesis by decreasing endothelial cell proliferation and migration, inducing endothelial cell apoptosis, and by decreasing VEGF production. However, activation of PPARγ by 15d-PGJ2 has been shown to upregulate VEGF expression in human breast cancer cells, which may contribute to increased tumor angiogenesis. Finally, PPARγ expression has been shown to be upregulated in stromal myofibroblasts surrounding colon adenocarcinomas, which promote proliferation, mobility, and invasion of tumor cells.