Stretching fibroblasts remodels fibronectin and alters cancer cell migration.
Stretching fibroblasts remodels fibronectin and alters cancer cell migration.
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DOI：
10.1038/srep08334
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发表时间：
2015-02-09
影响因子：
4.6
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Ao M;Brewer BM;Yang L;Franco Coronel OE;Hayward SW;Webb DJ;Li D
大多数癌症-基质相互作用的研究都集中在生化信号传导效应上，而对生物物理因素的关注要少得多。在这项研究中，我们使用微流体平台研究了机械刺激对人类前列腺成纤维细胞的作用，该平台适合我们的实验，并进一步开发用于多种测定中的可重复性能以及与高分辨率共聚焦显微镜的兼容性。结果表明，正常组织相关成纤维细胞 (NAF) 的机械拉伸会改变分泌的纤连蛋白的结构。具体来说，未拉伸的 NAF 以随机的网状排列沉积和组装纤连蛋白，而拉伸的 NAF 则产生具有更有组织、线性排列结构的基质。此外，拉伸的 NAF 表现出增强的以持久方式引导共培养癌细胞迁移的能力。此外，通过观察血小板源性生长因子受体α（PDGFRα）表达增加，我们发现拉伸NAF会触发复杂的生化信号事件。将这些行为与癌症相关成纤维细胞 (CAF) 的行为进行比较表明，观察到的拉伸 NAF 的表型与 CAF 相关的表型相似，表明机械应力是 NAF 激活和 CAF 发生的关键因素。
Most investigations of cancer-stroma interactions have focused on biochemical signaling effects, with much less attention being paid to biophysical factors. In this study, we investigated the role of mechanical stimuli on human prostatic fibroblasts using a microfluidic platform that was adapted for our experiments and further developed for both repeatable performance among multiple assays and for compatibility with high-resolution confocal microscopy. Results show that mechanical stretching of normal tissue-associated fibroblasts (NAFs) alters the structure of secreted fibronectin. Specifically, unstretched NAFs deposit and assemble fibronectin in a random, mesh-like arrangement, while stretched NAFs produce matrix with a more organized, linearly aligned structure. Moreover, the stretched NAFs exhibited an enhanced capability for directing co-cultured cancer cell migration in a persistent manner. Furthermore, we show that stretching NAFs triggers complex biochemical signaling events through the observation of increased expression of platelet derived growth factor receptor α (PDGFRα). A comparison of these behaviors with those of cancer-associated fibroblasts (CAFs) indicates that the observed phenotypes of stretched NAFs are similar to those associated with CAFs, suggesting that mechanical stress is a critical factor in NAF activation and CAF genesis.
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DOI：
10.1016/j.bjps.2013.08.002
发表时间：
2013-12-01
影响因子：
2.7
作者：
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期刊：
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DOI：
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发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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