Department of Biomedical Engineering, The University of Akron, Akron, OH, USA.
Biotechnol J. 2014 Mar;9(3):426-34. doi: 10.1002/biot.201300227. Epub 2013 Dec 19.
Migration of tumor cells is a fundamental event implicated in metastatic progression of cancer. Therapeutic compounds with the ability to inhibit the motility of cancer cells are critical for preventing cancer metastasis. Achieving this goal requires new technologies that enable high-throughput drug screening against migration of cancer cells and expedite drug discovery. We report an easy-to-implement, robotically operated, cell migration microtechnology with the capability of simultaneous screening of multiple compounds. The technology utilizes a fully biocompatible polymeric aqueous two-phase system to pattern a monolayer of cells containing a cell-excluded gap that serves as the migration niche. We adapted this technology to a standard 96-well plate format and parametrically optimized it to generate highly consistent migration niches. The analysis of migration is done automatically using computerized schemes. We use statistical metrics and show the robustness of this assay for drug screening and its sensitivity to identify effects of different drug compounds on migration of cancer cells. This technology can be employed in core centers, research laboratories, and pharmaceutical industries to evaluate the efficacy of compounds against migration of various types of metastatic cancer cells prior to expensive animal tests and thus, streamline anti-migratory drug screening.
肿瘤细胞的迁移是癌症转移进展中涉及的一个基本事件。具有抑制癌细胞迁移能力的治疗化合物对于预防癌症转移至关重要。实现这一目标需要新的技术,这些技术能够实现高通量针对癌细胞迁移的药物筛选,并加速药物发现。我们报告了一种易于实施的、机器人操作的、具有同时筛选多种化合物能力的细胞迁移微技术。该技术利用完全生物相容的聚合物双水相体系来设计单层细胞,其中包含一个细胞排斥的间隙,作为迁移龛。我们将这项技术改编成标准的 96 孔板格式,并对其进行参数优化,以产生高度一致的迁移龛。使用计算机化方案自动进行迁移分析。我们使用统计指标,并展示了该测定法在药物筛选中的稳健性及其对识别不同药物化合物对癌细胞迁移影响的敏感性。这项技术可以在核心中心、研究实验室和制药行业中使用,在昂贵的动物试验之前评估化合物对各种类型转移性癌细胞迁移的疗效,从而简化抗迁移药物筛选。