Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties.
Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties.
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DOI：
10.1371/journal.pone.0138065
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Beverly L
中科院分区：
文献类型：
--
作者：
Scherzer MT;Waigel S;Donninger H;Arumugam V;Zacharias W;Clark G;Siskind LJ;Soucy P;Beverly L
肺癌的低存活率在很大程度上可以归因于侵袭和扩散到全身的转移细胞。肿瘤微环境由多种细胞类型和非细胞成分组成。TME通过提供迁移线索和改变肿瘤细胞的性质，在转移性癌症的发展中发挥关键作用。细胞外基质(ECM)是TME的主要成分，已被证明在肿瘤进展过程中改变成分，促进癌细胞侵袭和远离原发癌灶的生存。虽然ECM影响肿瘤进展的命运是众所周知的，但关于癌细胞-ECM相互作用影响的分子机制却知之甚少。为了正确理解和预防肺癌的扩散，阐明这些机制是非常必要的。然而，通常的体外研究不会将这些相互作用纳入日常细胞培养分析。我们采用了一种模型，将脱细胞的人成纤维细胞来源的ECM作为肺腺癌细胞系生长的三维基质。在这里，我们描述了成纤维细胞基质对各种肺源性上皮细胞系特性的影响，包括癌细胞和未转化的细胞。这项工作强调了细胞-细胞外基质相互作用的重要性及其纳入体外实验的要求。成纤维细胞来源的ECM作为一种体外技术的实施将为研究人员提供一个重要的因素来操作，以更好地重建和研究TME。
Poor survival rates from lung cancer can largely be attributed to metastatic cells that invade and spread throughout the body. The tumor microenvironment (TME) is composed of multiple cell types, as well as non-cellular components. The TME plays a critical role in the development of metastatic cancers by providing migratory cues and changing the properties of the tumor cells. The Extracellular Matrix (ECM), a main component of the TME, has been shown to change composition during tumor progression, contributing to cancer cell invasion and survival away from the primary cancer site. Although the ECM is well-known to influence the fate of tumor progression, little is known about the molecular mechanisms that are affected by the cancer cell-ECM interactions. It is imperative that these mechanisms are elucidated in order to properly understand and prevent lung cancer dissemination. However, common in vitro studies do not incorporate these interactions into everyday cell culture assays. We have adopted a model that examines decellularized human fibroblast-derived ECM as a 3-dimensional substrate for growth of lung adenocarcinoma cell lines. Here, we have characterized the effect of fibroblast-derived matrices on the properties of various lung-derived epithelial cell lines, including cancerous and non-transformed cells. This work highlights the significance of the cell-ECM interaction and its requirement for incorporation into in vitro experiments. Implementation of a fibroblast-derived ECM as an in vitro technique will provide researchers with an important factor to manipulate to better recreate and study the TME.