Zicha Daniel
CEITEC - Central European Institute of Technology, Brno University of Technology, Purkyňova 656/123, 612 00, Brno, Czech Republic.
Institute of Physical Engineering, Faculty of Mechanical Engineering, Brno University of Technology, Technická 2, 616 69, Brno, Czech Republic.
Sci Rep. 2022 Jan 31;12(1):1621. doi: 10.1038/s41598-022-05307-7.
The incidence of death caused by cancer has been increasing worldwide. The growth of cancer cells is not the main problem. The majority of deaths are due to invasion and metastasis, where cancer cells actively spread from primary tumors. Our inbred rat model of spontaneous metastasis revealed dynamic phenotype changes in vitro correlating with the metastatic potential in vivo and led to a discovery of a metastasis suppressor, protein 4.1B, which affects their 2D motility on flat substrates. Subsequently, others confirmed 4.1B as metastasis suppressor using knock-out mice and patient data suggesting mechanism involving apoptosis. There is evidence that 2D motility may be differentially controlled to the 3D situation. Here we show that 4.1B affects cell motility in an invasion assay similarly to the 2D system, further supporting our original hypothesis that the role of 4.1B as metastasis suppressor is primarily mediated by its effect on motility. This is encouraging for the validity of the 2D analysis, and we propose Quantitative Phase Imaging with incoherent light source for rapid and accurate testing of cancer cell motility and growth to be of interest for personalized cancer treatment as illustrated in experiments measuring responses of human adenocarcinoma cells to selected chemotherapeutic drugs.
全球范围内,癌症致死率一直在上升。癌细胞的生长并非主要问题。大多数死亡是由侵袭和转移导致的,即癌细胞从原发性肿瘤处主动扩散。我们的近交系大鼠自发转移模型揭示了体外动态表型变化与体内转移潜能相关,并导致发现了一种转移抑制因子——蛋白4.1B,它影响癌细胞在平坦基质上的二维运动。随后,其他人使用基因敲除小鼠和患者数据证实4.1B是转移抑制因子,提示其机制涉及细胞凋亡。有证据表明,二维运动可能与三维情况受到不同的调控。在此我们表明,在侵袭实验中,4.1B对细胞运动的影响与二维系统类似,进一步支持了我们最初的假设,即4.1B作为转移抑制因子的作用主要是通过其对运动的影响介导的。这为二维分析的有效性提供了鼓舞,并且我们提出,利用非相干光源的定量相成像技术用于快速准确地检测癌细胞的运动和生长,对于个性化癌症治疗具有重要意义,如在测量人腺癌细胞对选定化疗药物反应的实验中所示。