表達(dá)固定氧化酶形式黃嘌呤氧化還原酶的定向敲入小鼠有利于腫瘤生長(zhǎng)

中文摘要：

黃嘌呤氧化還原酶與癌癥有關(guān)。然而，其可互變的兩種形式——黃嘌呤脫氫酶（XDH）和黃嘌呤氧化酶（XO）在腫瘤形成過(guò)程中的作用尚不清楚。在本研究中，我們生成了XDH穩(wěn)定型和XO鎖定型敲入（ki）小鼠以探討這個(gè)問(wèn)題。腫瘤移植后，XO ki小鼠的腫瘤生長(zhǎng)顯著高于野生型（WT）和XDH ki小鼠。血液系統(tǒng)中XO表達(dá)導(dǎo)致了這一效果。荷蘭Liposoma氯膦酸鹽脂質(zhì)體清除劑清除巨噬細(xì)胞后，腫瘤生長(zhǎng)減緩。在WT小鼠中采用XO ki巨噬細(xì)胞移植會(huì)增加腫瘤生長(zhǎng)。體外實(shí)驗(yàn)顯示，XO ki巨噬細(xì)胞產(chǎn)生更高水平的活性氧（ROS），這導(dǎo)致腫瘤中調(diào)節(jié)性T細(xì)胞（Tregs）增多。體內(nèi)阻斷ROS可減緩腫瘤生長(zhǎng)。總體而言，這些結(jié)果表明XO/XDH的平衡在腫瘤發(fā)展的免疫監(jiān)控中起重要作用。特異性抑制XO形式的策略可能在控制癌癥生長(zhǎng)中具有價(jià)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.

論文信息：

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

期刊名稱：Nature Communications

時(shí)間期卷：10, Article number:4904(2019)

在線時(shí)間：2019年10月28日

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

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除皮下接種CMT93小鼠結(jié)直腸癌細(xì)胞腫瘤細(xì)胞模型巨噬細(xì)胞，荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見(jiàn)刊于Nature Communications：表達(dá)固定氧化酶形式黃嘌呤氧化還原酶的定向敲入小鼠有利于腫瘤生長(zhǎng)。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除腫瘤模型巨噬細(xì)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.

材料和方法文獻(xiàn)截圖：