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

Details

Serval ID
serval:BIB_AB744ACBDD11
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth.
Journal
Nature communications
Author(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
Publication state
Published
Issued date
28/10/2019
Peer-reviewed
Oui
Volume
10
Number
1
Pages
4904
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
07/01/2020 12:54
Last modification date
21/01/2021 7:26
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