A three-dimensional in vitro model of tumor cell intravasation.

A three-dimensional in vitro model of tumor cell intravasation.
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DOI:
10.1039/c3ib40170g
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发表时间:
2014-06
期刊:
Integrative biology : quantitative biosciences from nano to macro
影响因子:
--
通讯作者:
George SC
George SC
中科院分区:
其他
文献类型:
--
作者:
Ehsan SM;Welch-Reardon KM;Waterman ML;Hughes CC;George SC

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转移是超过 90% 的人类癌症死亡的原因。转移过程的早期步骤包括:新血管的形成、上皮间质转化(EMT)的启动以及肿瘤细胞动员进入循环系统。人们正在努力利用三维体外培养模型来复制人类肿瘤组织的生理景观;然而,很少有系统能够捕获全方位真实、复杂的体内事件,例如新血管形成和内渗。在这里,我们介绍前血管化肿瘤(PVT)模型来研究实体瘤进展的早期事件。 PVT 球体由内皮细胞和肿瘤细胞组成,并嵌入含有成纤维细胞的纤维蛋白基质中。 PVT 模型促进血管形成的两种机制:基质中强大的发芽血管生成,以及球体内的连续血管化。此外,PVT模型能够使肿瘤细胞的内渗在低氧条件下增强,并且还依赖于关键的EMT转录因子Slug。 PVT 模型在体外模拟人类肿瘤方面取得了重大进展,并可能改善转移过程中事件的研究和靶向。
Metastasis is the cause of over 90% of all human cancer deaths. Early steps in the metastatic process include: the formation of new blood vessels, the initiation of epithelial-mesenchymal transition (EMT), and the mobilization of tumor cells into the circulation. There are ongoing efforts to replicate the physiological landscape of human tumor tissue using three-dimensional in vitro culture models; however, few systems are able to capture the full range of authentic, complex in vivo events such as neovascularization and intravasation. Here we introduce the Prevascularized Tumor (PVT) model to investigate early events of solid tumor progression. PVT spheroids are composed of endothelial and tumor cells, and are embedded in a fibrin matrix containing fibroblasts. The PVT model facilitates two mechanisms of vessel formation: robust sprouting angiogenesis into the matrix, and contiguous vascularization within the spheroid. Furthermore, the PVT model enables the intravasation of tumor cells that is enhanced under low oxygen conditions and is also dependent on the key EMT transcription factor Slug. The PVT model provides a significant advance in the mimicry of human tumors in vitro and may improve investigation and targeting of events in the metastatic process.
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