ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response.

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_067E71481B3F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response.
Périodique
Oncogene
Auteur(s)
Tan EHP, Sng M.K., How ISB, Chan JSK, Chen J., Tan C.K., Wahli W., Tan N.S.
ISSN
1476-5594 (Electronic)
ISSN-L
0950-9232
Statut éditorial
Publié
Date de publication
04/2018
Peer-reviewed
Oui
Volume
37
Numéro
15
Pages
2067-2078
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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 <sup>-/-</sup> mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d <sup>-/-</sup> mice developed fewer intestinal polyps and survived longer when compared with Pparb/d <sup>fl/fl</sup> mice. The pre-treatment of FSPCre-Pparb/d <sup>-/-</sup> and Pparb/d <sup>fl/fl</sup> 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 <sup>-/-</sup> intestinal tumors have reduced oxidative stress than Pparb/d <sup>fl/fl</sup> 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.
Mots-clé
Animals, Antioxidants/metabolism, Cells, Cultured, Epithelial Cells/drug effects, Epithelial Cells/metabolism, Fibroblasts/metabolism, Gene Knockdown Techniques, HCT116 Cells, HT29 Cells, Humans, Mice, Mice, Knockout, PPAR delta/genetics, PPAR-beta/genetics, Reactive Oxygen Species/metabolism, Reactive Oxygen Species/pharmacology, Tumor Burden/drug effects, Tumor Burden/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/02/2018 21:48
Dernière modification de la notice
20/08/2019 13:28
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