Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth.

Détails

Ressource 1Télécharger: 31659168_BIB_AB744ACBDD11.pdf (2290.24 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_AB744ACBDD11
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth.
Périodique
Nature communications
Auteur(s)
Kusano T., Ehirchiou D., Matsumura T., Chobaz V., Nasi S., Castelblanco M., So A., Lavanchy C., Acha-Orbea H., Nishino T., Okamoto K., Busso N.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
28/10/2019
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
4904
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Xanthine oxidoreductase has been implicated in cancer. Nonetheless, the role played by its two convertible forms, xanthine dehydrogenase (XDH) and oxidase (XO) during tumorigenesis is not understood. Here we produce XDH-stable and XO-locked knock-in (ki) mice to address this question. After tumor transfer, XO ki mice show strongly increased tumor growth compared to wild type (WT) and XDH ki mice. Hematopoietic XO expression is responsible for this effect. After macrophage depletion, tumor growth is reduced. Adoptive transfer of XO-ki macrophages in WT mice increases tumor growth. In vitro, XO ki macrophages produce higher levels of reactive oxygen species (ROS) responsible for the increased Tregs observed in the tumors. Blocking ROS in vivo slows down tumor growth. Collectively, these results indicate that the balance of XO/XDH plays an important role in immune surveillance of tumor development. Strategies that inhibit the XO form specifically may be valuable in controlling cancer growth.
Mots-clé
Animals, Cell Proliferation, Female, Gene Knock-In Techniques, Humans, Macrophages/enzymology, Macrophages/metabolism, Male, Mice, Mice, Inbred C57BL, Neoplasms/enzymology, Neoplasms/genetics, Neoplasms/metabolism, Neoplasms/physiopathology, Reactive Oxygen Species/metabolism, Xanthine Dehydrogenase/genetics, Xanthine Dehydrogenase/metabolism, Xanthine Oxidase/genetics, Xanthine Oxidase/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/01/2020 12:54
Dernière modification de la notice
30/04/2021 7:13
Données d'usage