Mechanisms of tumor cell extravasation in an in vitro microvascular network platform.
Mechanisms of tumor cell extravasation in an in vitro microvascular network platform.
复制标题
DOI：
10.1039/c3ib40149a
复制
发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Kamm RD
中科院分区：
文献类型：
--
作者：
Chen MB;Whisler JA;Jeon JS;Kamm RD
更深入地了解肿瘤细胞外渗的机制对于创造针对癌症转移这一关键步骤的治疗方法至关重要。在这里，我们使用微流控平台来研究肿瘤细胞在血管形成过程中从体外微血管网络外渗。我们展示了紧密的内皮细胞-细胞连接，基底膜沉积和血管通透性的生理价值。通过我们的实验，我们证明了内皮屏障功能受损和炎症细胞因子刺激下的外渗效率增加，以及MDA-MB-231、HT-1080、MCF-10A的转移潜力与其外渗能力之间的正相关。高分辨率延时显微镜揭示了外渗事件的高度动态性质，首先是薄薄的肿瘤细胞突出穿过内皮，然后通过在内皮屏障中形成小（~ 1 μm）的开口（~ 8 μm）挤压细胞体的其余部分，从而允许核转移。内皮细胞-细胞连接在60倍时未被破坏，或在完成迁移后局部屏障功能的改变。肿瘤在被困细胞中的跨内皮迁移效率明显高于未被困的粘附细胞，在细胞簇中也明显高于单个肿瘤细胞。
A deeper understanding of the mechanisms of tumor cell extravasation is essential in creating therapies that target this crucial step in cancer metastasis. Here, we use a microfluidic platform to study tumor cell extravasation fromin vitromicrovascular networks formedviavasculogenesis. We demonstrate tight endothelial cell–cell junctions, basement membrane deposition and physiological values of vessel permeability. Employing our assay, we demonstrate impaired endothelial barrier function and increased extravasation efficiency with inflammatory cytokine stimulation, as well as positive correlations between the metastatic potentials of MDA-MB-231, HT-1080, MCF-10A and their extravasation capabilities. High-resolution time-lapse microscopy reveals the highly dynamic nature of extravasation events, beginning with thin tumor cell protrusions across the endothelium followed by extrusion of the remainder of the cell body through the formation of small (∼1 μm) openings in the endothelial barrier which grows in size (∼8 μm) to allow for nuclear transmigration. No disruption to endothelial cell–cell junctions is discernible at 60×, or by changes in local barrier function after completion of transmigration. Tumor transendothelial migration efficiency is significantly higher in trapped cells compared to non-trapped adhered cells, and in cell clustersversussingle tumor cells.
登录
查看更多内容
影响因子：
3.7
作者：
DIMILLA, PA;QUINN, JA;LAUFFENBURGER, DA
通讯作者：
LAUFFENBURGER, DA
DOI：
10.1007/s00432-002-0377-7
发表时间：
2002-10-01
影响因子：
3.6
作者：
Heyder, C;Gloria-Maercker, E;Dittmar, T
通讯作者：
Dittmar, T
影响因子：
7.5
作者：
Nicolson, G. L.
通讯作者：
Nicolson, G. L.
影响因子：
6.1
作者：
Kim, Sudong;Lee, Hyunjae;Jeon, Noo Li
通讯作者：
Jeon, Noo Li
实时成像揭示脑转移瘤形成的单一步骤
影响因子：
82.9
作者：
Kienast, Yvonne;von Baumgarten, Louisa;Winkler, Frank
通讯作者：
Winkler, Frank