Using real-time impedance-based assays to monitor the effects of fibroblast-derived media on the adhesion, proliferation, migration and invasion of colon cancer cells.
Using real-time impedance-based assays to monitor the effects of fibroblast-derived media on the adhesion, proliferation, migration and invasion of colon cancer cells.
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DOI：
10.1042/bsr20140031
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发表时间：
2014-07-29
影响因子：
4
通讯作者：
Kiely PA
中科院分区：
文献类型：
--
作者：
Dowling CM;Herranz Ors C;Kiely PA
增加我们对调控细胞增殖、迁移和侵袭机制的了解是理解肿瘤进展和转移的核心。局部肿瘤微环境通过提供改变细胞行为和促进转移的特定环境线索，对癌症的转化表型做出贡献。成纤维细胞与癌症有很强的相关性，近年来，人们在设计改变肿瘤微环境中成纤维细胞行为的新治疗策略方面受到了一些重视。成纤维细胞产生生长因子、趋化因子和许多沉积在ECM(细胞外基质)中的蛋白质，促进血管生成、炎症和肿瘤进展。在这项研究中，我们使用一个无标记的RTCA(实时细胞分析)平台(XCELLigence)来研究来自人成纤维细胞的培养液如何改变癌细胞的行为。我们使用了一系列免费的和新颖的实验方法来展示HCT116细胞在人成纤维细胞培养液存在的情况下黏附、增殖和迁移的速度显著加快。此外，我们使用xCELLigence CIM-PLATES系统显示，当HCT116细胞向来自人成纤维细胞的培养液迁移时，HCT116细胞侵袭基质层。这些数据有力地表明成纤维细胞有能力增加HCT116细胞的迁移和侵袭特性。这是第一个提供成纤维细胞介导的结肠癌细胞迁移和侵袭动力学实时数据的研究。在这里，我们使用RTCA平台来评估结肠癌细胞在来自成纤维细胞的培养液中的黏附、增殖、迁移和侵袭的动力学。这项工作强调了在癌症治疗中考虑间质环境的重要性。
Increasing our knowledge of the mechanisms regulating cell proliferation, migration and invasion are central to understanding tumour progression and metastasis. The local tumour microenvironment contributes to the transformed phenotype in cancer by providing specific environmental cues that alter the cells behaviour and promotes metastasis. Fibroblasts have a strong association with cancer and in recent times there has been some emphasis in designing novel therapeutic strategies that alter fibroblast behaviour in the tumour microenvironment. Fibroblasts produce growth factors, chemokines and many of the proteins laid down in the ECM (extracellular matrix) that promote angiogenesis, inflammation and tumour progression. In this study, we use a label-free RTCA (real-time cell analysis) platform (xCELLigence) to investigate how media derived from human fibroblasts alters cancer cell behaviour. We used a series of complimentary and novel experimental approaches to show HCT116 cells adhere, proliferate and migrate significantly faster in the presence of media from human fibroblasts. As well as this, we used the xCELLigence CIM-plates system to show that HCT116 cells invade matrigel layers aggressively when migrating towards media derived from human fibroblasts. These data strongly suggest that fibroblasts have the ability to increase the migratory and invasive properties of HCT116 cells. This is the first study that provides real-time data on fibroblast-mediated migration and invasion kinetics of colon cancer cells. Here, we use an RTCA platform to assess the kinetics of colon cancer cell adhesion, proliferation, migration and invasion in response to media derived from fibroblasts. This work highlights the importance of considering the stromal environment in cancer treatment.