The invasion of malignant cells into tissue is a critical step in the progression of cancer. While it is increasingly appreciated that cells within a tumor differ in their invasive potential, it remains nearly unknown how these differences relate to cell-to-cell variations in protein expression. Here, we introduce a microfluidic platform that integrates measurements of invasive motility and protein expression for single cells, which we use to scrutinize human glioblastoma tumor-initiating cells (TICs). Our live-cell imaging microdevice is comprised of polyacrylamide microchannels that exhibit tissue-like stiffness and present chemokine gradients along each channel. Due to intrinsic differences in motility, cell subpopulations separate along the channel axis. The separated cells are then lysed in situ and each single-cell lysate is subjected to western blotting in the surrounding polyacrylamide matrix. We observe correlations between motility and Nestin and EphA2 expression. We identify protein–protein correlations within single TICs, which would be obscured with population-based assays. The integration of motility traits with single-cell protein analysis – on the same cell – offers a new means to identify druggable targets of invasive capacity.

中文翻译：

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将侵袭力与单个肿瘤细胞中的蛋白质表达联系起来†

恶性细胞侵入组织是癌症进展中的关键步骤。尽管人们越来越认识到肿瘤内的细胞的侵袭潜力不同，但这些差异如何与蛋白质表达中的细胞间差异相关仍然几乎是未知的。在这里，我们介绍了一种微流控平台，该平台整合了单个细胞的侵袭性运动和蛋白质表达的测量结果，可用于检查人胶质母细胞瘤肿瘤起始细胞（TICs）。我们的活细胞成像微设备由聚丙烯酰胺微通道组成，这些聚丙烯通道显示出类似组织的刚度，并沿每个通道呈现趋化因子梯度。由于运动性的内在差异，细胞亚群沿通道轴分离。然后将分离的细胞原位裂解然后将每个单细胞裂解物在周围的聚丙烯酰胺基质中进行western印迹分析。我们观察到运动性与Nestin和EphA2表达之间的相关性。我们确定了单个TIC中的蛋白质之间的相关性，而基于人群的检测方法会掩盖这些相关性。在同一细胞上将运动性状与单细胞蛋白质分析相结合，提供了一种新的手段来确定侵袭能力的可治疗靶标。