Modeling and quantification of cancer cell invasion through collagen type I matrices

Modeling and quantification of cancer cell invasion through collagen type I matrices
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DOI:
10.1387/ijdb.092948ow
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发表时间:
2010-01-01
影响因子:
0.7
通讯作者:
Bracke, Marc
Bracke, Marc
中科院分区:
生物学4区
文献类型:
--
作者:
De Wever, Olivier;Hendrix, An;Bracke, Marc

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肿瘤侵袭是癌细胞和基质环境之间复杂相互作用的结果。考虑到基质环境的贡献,我们开发了一种无膜单细胞和基于球体的互补模型来研究通过天然I型胶原基质的癌症侵袭。细胞形态在试验期间得以保存,从而允许真实的时间监测侵袭诱导的细胞结构和F-肌动蛋白组织的变化。将这些模型与计算机定量相结合,可以计算出高度可重复的和操作员独立的数据。这些测定在使用荧光探针方面是通用的,并且具有灵活的动力学终点。一旦根据经验确定了最佳实验条件,I型胶原侵袭测定可用于靶向侵袭的小分子抑制剂的临床前验证。单细胞和球体侵袭模型的启动和监测可分别在8 h(超过3天)和14 h(超过8天)内实现。
Tumor invasion is the outcome of a complex interplay between cancer cells and the stromal environment. Considering the contribution of the stromal environment, we developed a membrane-free single-cell and spheroid based complementary model to study cancer invasion through native collagen type-I matrices. Cell morphology is preserved during the assays allowing real time monitoring of invasion-induced changes in cell structure and F-actin organization. Combining these models with computerized quantification permits the calculation of highly reproducible and operator-independent data. These assays are versatile in the use of fluorescent probes and have a flexible kinetic endpoint. Once the optimal experimental conditions are empirically determined, the collagen type-I invasion assays can be used for preclinical validation of small-molecule inhibitors targeting invasion. Initiation and monitoring of the single-cell and spheroid invasion model can be achieved in 8 h (over 3 days) and in 14 h (over 8 days) respectively.