| First Author | Cheng WY | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27692066 | Mgi Jnum | J:238498 |
| Mgi Id | MGI:5822946 | Doi | 10.7554/eLife.18501 |
| Citation | Cheng WY, et al. (2016) Macrophage PPARgamma inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone. Elife 5:e18501 |
| abstractText | Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARgamma loss-of-function mutations, but inhibited by PPARgamma agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARgamma tumor-suppressive functions. Here we report that macrophage PPARgamma deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARgamma target in macrophage whose expression is enhanced by PPARgamma loss but repressed by PPARgamma activation. Functionally, macrophage Gpr132 is pro-inflammatory and pro-tumor. Genetic Gpr132 deletion not only retards inflammation and cancer growth but also abrogates the anti-tumor effects of PPARgamma and rosiglitazone. Pharmacological Gpr132 inhibition significantly impedes mammary tumor malignancy. These findings uncover macrophage PPARgamma and Gpr132 as critical TAM modulators, new cancer therapeutic targets, and essential mediators of TZD anti-cancer effects. |
