A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer

波形蛋白 生物 上皮-间质转换 病理 癌症研究 间充质干细胞 鼻涕虫 循环肿瘤细胞 原发性肿瘤 转移 体内 癌症 免疫组织化学 免疫学 医学 细胞生物学 生物技术 遗传学
作者
Arnaud Bonnomet,Laïdya Syne,Anne Brysse,Émilie Feyereisen,Erik W. Thompson,Agnès Noël,J.M. Foidart,Philippe Birembaut,Myriam Polette,Christine Gilles
出处
期刊:Oncogene [Springer Nature]
卷期号:31 (33): 3741-3753 被引量:173
标识
DOI:10.1038/onc.2011.540
摘要

Epithelial-to-mesenchymal transition (EMT) processes endow epithelial cells with enhanced migratory/invasive properties and are therefore likely to contribute to tumor invasion and metastatic spread. Because of the difficulty in following EMT processes in human tumors, we have developed and characterized an animal model with transplantable human breast tumor cells (MDA-MB-468) uniquely showing spontaneous EMT events to occur. Using vimentin as a marker of EMT, heterogeneity was revealed in the primary MDA-MB-468 xenografts with vimentin-negative and vimentin-positive areas, as also observed on clinical human invasive breast tumor specimens. Reverse transcriptase-PCR after microdissection of these populations from the xenografts revealed EMT traits in the vimentin-positive zones characterized by enhanced 'mesenchymal gene' expression (Snail, Slug and fibroblast-specific protein-1) and diminished expression of epithelial molecules (E-cadherin, ZO-3 and JAM-A). Circulating tumor cells (CTCs) were detected in the blood as soon as 8 days after s.c. injection, and lung metastases developed in all animals injected as examined by in vivo imaging analyses and histology. High levels of vimentin RNA were detected in CTCs by reverse transcriptase-quantitative PCR as well as, to a lesser extent, Snail and Slug RNA. Von Willebrand Factor/vimentin double immunostainings further showed that tumor cells in vascular tumoral emboli all expressed vimentin. Tumoral emboli in the lungs also expressed vimentin whereas macrometastases displayed heterogenous vimentin expression, as seen in the primary xenografts. In conclusion, our data uniquely demonstrate in an in vivo context that EMT occurs in the primary tumors, and associates with an enhanced ability to intravasate and generate CTCs. They further suggest that mesenchymal-to-epithelial phenomena occur in secondary organs, facilitating the metastatic growth.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
wanci应助一个小胖子采纳,获得10
刚刚
2秒前
烟花应助聪明可爱小绘理采纳,获得10
3秒前
一颗西柚完成签到 ,获得积分10
6秒前
细心妙旋完成签到 ,获得积分10
7秒前
清城发布了新的文献求助10
7秒前
8秒前
9秒前
9秒前
我是老大应助欢喜采纳,获得10
11秒前
12秒前
12秒前
14秒前
所所应助坛坛采纳,获得20
14秒前
JamesPei应助清城采纳,获得10
15秒前
秋辞完成签到,获得积分10
16秒前
17秒前
杳鸢应助Bonner采纳,获得10
17秒前
17秒前
17秒前
18秒前
科研通AI2S应助hanbing采纳,获得10
19秒前
铜锣湾小研仔应助eff采纳,获得10
20秒前
20秒前
JamesPei应助贺兰生羽采纳,获得10
20秒前
21秒前
飞飛飝完成签到,获得积分10
21秒前
jiujiudejian发布了新的文献求助10
22秒前
wiwin发布了新的文献求助10
23秒前
诗瑜发布了新的文献求助10
23秒前
清颜发布了新的文献求助20
24秒前
26秒前
27秒前
见青山应助科研通管家采纳,获得10
28秒前
怕黑冰安应助科研通管家采纳,获得10
28秒前
见青山应助科研通管家采纳,获得10
28秒前
大模型应助科研通管家采纳,获得10
28秒前
劲秉应助科研通管家采纳,获得10
28秒前
见青山应助科研通管家采纳,获得10
28秒前
充电宝应助wiwin采纳,获得10
28秒前
高分求助中
Licensing Deals in Pharmaceuticals 2019-2024 3000
Effect of reactor temperature on FCC yield 2000
Very-high-order BVD Schemes Using β-variable THINC Method 1020
Impiego dell’associazione acetazolamide/pentossifillina nel trattamento dell’ipoacusia improvvisa idiopatica in pazienti affetti da glaucoma cronico 900
錢鍾書楊絳親友書札 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
Mission to Mao: Us Intelligence and the Chinese Communists in World War II 600
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3297370
求助须知:如何正确求助?哪些是违规求助? 2932791
关于积分的说明 8459401
捐赠科研通 2605608
什么是DOI,文献DOI怎么找? 1422424
科研通“疑难数据库(出版商)”最低求助积分说明 661383
邀请新用户注册赠送积分活动 644710