国产精品九九热-国产精品九九免费视频-国产精品九九九久久九九-国产精品精品视频-国产精品精品国产-国产精品精品

技術(shù)文章您現(xiàn)在的位置:首頁 > 技術(shù)文章 > Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除巨噬細(xì)胞骨肉瘤模型腫瘤免疫研究

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除巨噬細(xì)胞骨肉瘤模型腫瘤免疫研究

更新時間:2025-03-05   點(diǎn)擊次數(shù):157次

中文摘要:

化療通過尚不明確的機(jī)制引發(fā)腫瘤免疫逃逸。本研究發(fā)現(xiàn),化療顯著上調(diào)骨肉瘤組織中CD47的表達(dá)水平,且其表達(dá)水平與患者死亡率呈正相關(guān)。我們揭示了化療誘導(dǎo)的巨噬細(xì)胞通過分泌白細(xì)胞介素-18(IL-18),促使腫瘤細(xì)胞上調(diào)L-氨基酸轉(zhuǎn)運(yùn)蛋白2(LAT2)的表達(dá),從而顯著增強(qiáng)對亮氨酸和谷氨酰胺這兩種mTORC1強(qiáng)效激活劑的攝取。升高的亮氨酸水平與增強(qiáng)的谷氨酰胺分解代謝共同激活mTORC1信號通路,進(jìn)而通過c-Myc介導(dǎo)CD47的轉(zhuǎn)錄。抑制LAT2表達(dá)或使用LAT抑制劑處理腫瘤細(xì)胞可下調(diào)CD47,同時增強(qiáng)巨噬細(xì)胞對腫瘤細(xì)胞的浸潤和吞噬能力,使骨肉瘤小鼠模型對阿霉素治療更為敏感。這些發(fā)現(xiàn)揭示了巨噬細(xì)胞與腫瘤細(xì)胞間的雙向調(diào)控機(jī)制在腫瘤免疫逃逸中的關(guān)鍵作用,并提示通過干預(yù)LAT2介導(dǎo)的氨基酸攝取通路可能為優(yōu)化癌癥治療提供新策略。

英文摘要:

Chemotherapy elicits tumor immune evasion with poorly characterized mechanisms. Here, we demonstrate that chemotherapy markedly enhances the expression levels of CD47 in osteosarcoma tissues, which are positively associated with patient mortality. We reveal that macrophages in response to chemotherapy secrete interleukin-18, which in turn upregulates expression of L-amino acid transporter 2 (LAT2) in tumor cells for substantially enhanced uptakes of leucine and glutamine, two potent stimulators of mTORC1. The increased levels of leucine and enhanced glutaminolysis activate mTORC1 and subsequent c-Myc-mediated transcription of CD47. Depletion of LAT2 or treatment of tumor cells with a LAT inhibitor downregulates CD47 with enhanced macrophage infiltration and phagocytosis of tumor cells, and sensitizes osteosarcoma to doxorubicin treatment in mice. These findings unveil a mutual regulation between macrophage and tumor cells that plays a critical role in tumor immune evasion and underscore the potential to intervene with the LAT2-mediated amino acid uptake for improving cancer therapies.


論文信息:

論文題目:

Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion

期刊名稱:Nature Communications

時間期卷:13, Article number: 6308 (2022)

在線時間:2022年10月23日

DOI:doi.org/10.1038/s41467-022-34064-4

產(chǎn)品信息:

貨號:CP-005-005

規(guī)格:5ml+5ml

品牌:Liposoma

產(chǎn)地:荷蘭

名稱:Clodronate Liposomes and Control Liposomes

辦事處:Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體助力骨肉瘤模型研究,荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications


氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞助力骨肉瘤模型腫瘤免疫研究

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除巨噬細(xì)胞骨肉瘤模型腫瘤免疫研究


Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法:

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除巨噬細(xì)胞骨肉瘤模型腫瘤免疫研究


Macrophage depletion by clodronate liposomes

For macrophage depletion, 200?μL clodronate liposomes (Liposoma B.V.) or PBS liposomes (Liposoma B.V.) were administered through the caudal vein 3 days prior to tumor injection and every 4 days (seven times in total). BCH was administered intravenously at 200?mg/kg per mouse the day after the first doxorubicin treatment, then every 2 days, four times. Intraperitoneal injections of CD47 mAb (Bio X cell) at a dose of 10?mg/kg was initiated the day after the first doxorubicin treatment, then every 2 days for four times. 2?×?106 SJSA-1 cells, GFP+ SJSA-1 cells, shCtrl SJSA-1 cells or shIL18R1 SJSA-1 cells were subcutaneously injected into BALB/c nude mice on day 0. Doxorubicin (5?mg/kg) was injected intraperitoneally five times every 3 days after tumor grew for 2 weeks. BCH (200?mg/kg) was injected intravenously after first doxorubicin treatment, and then every 2 days for 7 times. Clodronate liposomes were administered through the caudal vein 3 days prior to tumor injection and every 4 days for a total of nine times. Tumors were measured at indicated times and tumor volume was calculated using the formula: π/6?×?length?×?width.

靶點(diǎn)科技(北京)有限公司

靶點(diǎn)科技(北京)有限公司

地址:中關(guān)村生命科學(xué)園北清創(chuàng)意園2-4樓2層

© 2025 版權(quán)所有:靶點(diǎn)科技(北京)有限公司  備案號:京ICP備18027329號-2  總訪問量:294443  站點(diǎn)地圖  技術(shù)支持:化工儀器網(wǎng)  管理登陸

主站蜘蛛池模板: 绿巨人香蕉草莓丝瓜茄子番茄在线 | 国产资源精品一区二区免费 | 污视频网站在线观看免费 | 99热婷婷| 亚洲国产精品一区二区久久 | 手机看片中文字幕 | 99国产高清久久久久久网站 | 看一级毛片免费观看视频 | 在线免费观看欧美大片 | 亚洲免费网站 | 四虎国产精品一区二区 | 朋友的妻子 在线播放 | 日韩黄色一级 | 婷婷综合久久中文字幕蜜桃三 | 天天影视色香欲综合网 寡妇 | 在线观看h视频 | 精品卡1卡2卡三卡免费网站 | 在线观看视频色 | 色综合久久久久久久 | 天天se天天cao综合网蜜芽 | 日韩中文字幕视频在线观看 | 一级做性色a爱片久久片 | 粉嫩极品国产在线播放 | 欧美在线观看视频一区 | 国产乱码一区二区三区四区 | 狠狠干天天操 | 欧色视频 | 日韩欧美在线视频 | 老司机免费精品视频 | 欧美日韩免费看 | 国内自拍视频在线播放 | 最新香蕉97超级碰碰碰碰碰久 | 欧美在线观看不卡 | 免费观看男女羞羞的视频网站 | 国产亚洲一欧美一区二区三区 | 日本黄在线观看免费播放 | 日本九九精品一区二区 | 蜜柚视频免费版在线看 | 99热这里只有精品久久免费 | 国产精品一区二区三 | 日本天堂在线视频 |