Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth
| العنوان: | Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth |
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| المؤلفون: | Alexander So, Mariela Castelblanco, Hans Acha-Orbea, Tomohiro Matsumura, Véronique Chobaz, Nathalie Busso, Teruo Kusano, Takeshi Nishino, Driss Ehirchiou, Ken Okamoto, Sonia Nasi, Christine Lavanchy |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature communications, vol. 10, no. 1, pp. 4904 Nature Communications |
| بيانات النشر: | Nature Portfolio, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Xanthine Oxidase, Adoptive cell transfer, Xanthine Dehydrogenase, Science, General Physics and Astronomy, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Gene knockin, medicine, Animals, Humans, Gene Knock-In Techniques, lcsh:Science, Cell Proliferation, Cancer, chemistry.chemical_classification, Oxidase test, Reactive oxygen species, Multidisciplinary, Chemistry, Cell growth, Macrophages, Wild type, General Chemistry, Female, Macrophages/enzymology, Macrophages/metabolism, 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, 030104 developmental biology, Xanthine dehydrogenase, 030220 oncology & carcinogenesis, Cancer research, Tumour immunology, lcsh:Q, Reactive Oxygen Species, Carcinogenesis |
| الوصف: | 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. The roles of the convertible forms, xanthine dehydrogenase (XDH) and xanthine oxidase (XO) during tumorigenesis is not known. Here, the authors develop XDH-stable and XO-locked knock-in (ki) mice and show increased tumor growth in XO ki mice, via macrophage-mediated immunoregulatory responses. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64bc8d18e5e6e17285be9cac5cbdc0f2Test https://doaj.org/article/a917fab180ef4bcfad65767813174f1dTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....64bc8d18e5e6e17285be9cac5cbdc0f2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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