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

Teruo Kusano, Driss Ehirchiou, Tomohiro Matsumura, Veronique Chobaz, Sonia Nasi, Mariela Castelblanco, Alexander So, Christine Lavanchy, Hans Acha-Orbea (), Takeshi Nishino, Ken Okamoto () and Nathalie Busso ()
Additional contact information
Teruo Kusano: Nippon Medical School
Driss Ehirchiou: University of Lausanne
Tomohiro Matsumura: Nippon Medical School
Veronique Chobaz: University of Lausanne, CHUV
Sonia Nasi: University of Lausanne, CHUV
Mariela Castelblanco: University of Lausanne, CHUV
Alexander So: University of Lausanne, CHUV
Christine Lavanchy: University of Lausanne
Hans Acha-Orbea: University of Lausanne
Takeshi Nishino: Nippon Medical School
Ken Okamoto: Nippon Medical School
Nathalie Busso: University of Lausanne, CHUV

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12565-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12565-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12565-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().