| First Author | Tan EHP | Year | 2018 |
| Journal | Oncogene | Volume | 37 |
| Issue | 15 | Pages | 2067-2078 |
| PubMed ID | 29367760 | Mgi Jnum | J:261041 |
| Mgi Id | MGI:6153459 | Doi | 10.1038/s41388-017-0109-8 |
| Citation | Tan EHP, et al. (2018) ROS release by PPARbeta/delta-null fibroblasts reduces tumor load through epithelial antioxidant response. Oncogene 37(15):2067-2078 |
| abstractText | Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARbeta/delta in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARbeta/delta, using a FSPCre-Pparb/d(-/-) mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d(-/-) mice developed fewer intestinal polyps and survived longer when compared with Pparb/d(fl/fl) mice. The pre-treatment of FSPCre-Pparb/d(-/-) and Pparb/d(fl/fl) with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load. Gene expression analyses implicated an altered oxidative stress processes. Indeed, the FSPCre-Pparb/d(-/-) intestinal tumors have reduced oxidative stress than Pparb/d(fl/fl) tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARbeta/delta expression. Therefore, our results establish a role for fibroblast PPARbeta/delta in epithelial-mesenchymal communication for ROS homeostasis. |
