Differential response of patient-derived primary glioblastoma cells to environmental stiffness.
Differential response of patient-derived primary glioblastoma cells to environmental stiffness.
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DOI：
10.1038/srep23353
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发表时间：
2016-03-21
影响因子：
4.6
通讯作者：
O'Neill GM
中科院分区：
文献类型：
--
作者：
Grundy TJ;De Leon E;Griffin KR;Stringer BW;Day BW;Fabry B;Cooper-White J;O'Neill GM
癌细胞感知外部机械力的能力已经成为促进癌症侵袭的重要因素。目前，关于胶质母细胞瘤（GBM）脑癌细胞迁移和侵袭是否对刚性敏感，文献中有相互矛盾的报道。为了解决这个问题，我们比较了原发性患者源性GBM系的刚性反应。将细胞接种在反映脑组织力学环境多样性的确定刚度的聚丙烯酰胺凝胶上，并通过延时显微镜分析细胞形态和迁移。在包埋在3D基质胶培养物中的多细胞球体中评估侵袭性。我们的数据揭示了一系列的刚度依赖性的反应之间的患者来源的细胞系，从减少迁移的最顺应性的组织刚度的那些是不敏感的基板刚度和同样的迁移，无论底层的基板刚度。值得注意的是，刚性不敏感的GBM细胞在软3D基质胶培养中显示出最大的侵袭能力。总的来说，我们的数据证实了原代GBM患者来源的细胞的刚性依赖性和独立性行为。
The ability of cancer cells to sense external mechanical forces has emerged as a significant factor in the promotion of cancer invasion. Currently there are conflicting reports in the literature with regard to whether glioblastoma (GBM) brain cancer cell migration and invasion is rigidity-sensitive. In order to address this question we have compared the rigidity-response of primary patient-derived GBM lines. Cells were plated on polyacrylamide gels of defined rigidity that reflect the diversity of the brain tissue mechanical environment, and cell morphology and migration were analysed by time-lapse microscopy. Invasiveness was assessed in multicellular spheroids embedded in 3D matrigel cultures. Our data reveal a range of rigidity-dependent responses between the patient-derived cell lines, from reduced migration on the most compliant tissue stiffness to those that are insensitive to substrate rigidity and are equally migratory irrespective of the underlying substrate stiffness. Notably, the rigidity-insensitive GBM cells show the greatest invasive capacity in soft 3D matrigel cultures. Collectively our data confirm both rigidity-dependent and independent behaviour in primary GBM patient-derived cells.