Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Department of Prosthodontics, Preclinical Education and Material Sciences, University Hospital, Medical Faculty, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany.
Int J Mol Sci. 2021 Nov 4;22(21):11961. doi: 10.3390/ijms222111961.
Staurosporine-dependent single and collective cell migration patterns of breast carcinoma cells MDA-MB-231, MCF-7, and SK-BR-3 were analysed to characterise the presence of drug-dependent migration promoting and inhibiting yin-yang effects.
Migration patterns of various breast cancer cells after staurosporine treatment were investigated using Western blot, cell toxicity assays, single and collective cell migration assays, and video time-lapse. Statistical analyses were performed with Kruskal-Wallis and Fligner-Killeen tests.
Application of staurosporine induced the migration of single MCF-7 cells but inhibited collective cell migration. With the exception of low-density SK-BR-3 cells, staurosporine induced the generation of immobile flattened giant cells. Video time-lapse analysis revealed that within the borderline of cell collectives, staurosporine reduced the velocity of individual MDA-MB-231 and SK-BR-3, but not of MCF-7 cells. In individual MCF-7 cells, mainly the directionality of migration became disturbed, which led to an increased migration rate parallel to the borderline, and hereby to an inhibition of the migration of the cell collective as a total. Moreover, the application of staurosporine led to a transient activation of ERK1/2 in all cell lines.
Dependent on the context (single versus collective cells), a drug may induce opposite effects in the same cell line.
分析依赖于星形孢菌素的乳腺癌细胞 MDA-MB-231、MCF-7 和 SK-BR-3 的单细胞和群体细胞迁移模式,以表征药物依赖性促进和抑制迁移的阴阳效应的存在。
使用 Western blot、细胞毒性测定、单细胞和群体细胞迁移测定以及视频延时来研究各种乳腺癌细胞在星形孢菌素处理后的迁移模式。使用 Kruskal-Wallis 和 Fligner-Killeen 检验进行统计分析。
星形孢菌素的应用诱导了 MCF-7 细胞的迁移,但抑制了群体细胞的迁移。除了低密度的 SK-BR-3 细胞外,星形孢菌素诱导了不活动的扁平巨细胞的产生。视频延时分析显示,在细胞群体的边界内,星形孢菌素降低了 MDA-MB-231 和 SK-BR-3 细胞的个体速度,但不降低 MCF-7 细胞的速度。在单个 MCF-7 细胞中,主要是迁移的方向性受到干扰,这导致平行于边界的迁移率增加,并因此抑制了细胞群体的总迁移。此外,星形孢菌素的应用导致所有细胞系中 ERK1/2 的短暂激活。
依赖于上下文(单细胞与群体细胞),同一细胞系中的药物可能会产生相反的作用。