表达固定氧化酶形式黄嘌呤氧化还原酶的定向敲入小鼠有利于肿瘤生长

中文摘要：

黄嘌呤氧化还原酶与癌症有关。然而，其可互变的两种形式——黄嘌呤脱氢酶（XDH）和黄嘌呤氧化酶（XO）在肿瘤形成过程中的作用尚不清楚。在本研究中，我们生成了XDH稳定型和XO锁定型敲入（ki）小鼠以探讨这个问题。肿瘤移植后，XO ki小鼠的肿瘤生长显著高于野生型（WT）和XDH ki小鼠。血液系统中XO表达导致了这一效果。荷兰Liposoma氯膦酸盐脂质体清除剂清除巨噬细胞后，肿瘤生长减缓。在WT小鼠中采用XO ki巨噬细胞移植会增加肿瘤生长。体外实验显示，XO ki巨噬细胞产生更高水平的活性氧（ROS），这导致肿瘤中调节性T细胞（Tregs）增多。体内阻断ROS可减缓肿瘤生长。总体而言，这些结果表明XO/XDH的平衡在肿瘤发展的免疫监控中起重要作用。特异性抑制XO形式的策略可能在控制癌症生长中具有价值。

英文摘要：

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.

论文信息：

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

期刊名称：Nature Communications

时间期卷：10, Article number:4904(2019)

在线时间：2019年10月28日

DOI： doi.org/10.1038/s41467-019-12565-z

产品信息：

货号：CP-005-005

规格：5ml+5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes&Control liposomes

办事处：Target Technology(靶点科技)

Clodronate Liposomes氯膦酸盐脂质体清除皮下接种CMT93小鼠结直肠癌细胞肿瘤细胞模型巨噬细胞，荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Nature Communications：表达固定氧化酶形式黄嘌呤氧化还原酶的定向敲入小鼠有利于肿瘤生长。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除肿瘤模型巨噬细胞的材料和方法：

In vivo macrophage depletion

Liposome-encapsulated clodronate (dichloromethylene bisphosphonate) or liposome-PBS were provided by LIPOSOMA, Amsterdam, Netherlands, and were prepared according to the manufacturer’s protocol. Mice were daily injected intraperitoneally with 200 μL of a clodronate-loaded liposome suspension 4 times starting 3 days before tumor injection. Control mice were injected with 200 μL PBS-loaded liposomes using the same schedule.

材料和方法文献截图：