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Title: ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response
Authors: Tan, Eddie Han Pin
Sng, Ming Keat
How, Ivan Shun Bo
Chan, Jeremy Soon Kiat
Chen, Jiapeng
Tan, Chek Kun
Wahli, Walter
Tan, Nguan Soon
Keywords: Reactive Oxygen Species
DRNTU::Science::Biological sciences
Colorectal Cancer
Issue Date: 2018
Source: Tan, E. H. P., Sng, M. K., How, I. S. B., Chan, J. S. K., Chen, J., Tan, C. K., . . . Tan, N. S. (2018). ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response. Oncogene, 37(15), 2067-2078. doi:10.1038/s41388-017-0109-8
Series/Report no.: Oncogene
Abstract: 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 PPARβ/δ 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 PPARβ/δ, 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/dfl/fl mice. The pre-treatment of FSPCre-Pparb/d−/− and Pparb/dfl/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/dfl/fl tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARβ/δ expression. Therefore, our results establish a role for fibroblast PPARβ/δ in epithelial–mesenchymal communication for ROS homeostasis.
ISSN: 0950-9232
DOI: 10.1038/s41388-017-0109-8
Rights: © 2018 The Author(s). This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
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