Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce, Urla, Izmir, Turkey.
Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Izmir, İnciralti, Turkey.
J Cell Mol Med. 2024 Oct;28(19):e70105. doi: 10.1111/jcmm.70105.
Understanding the mechanisms by which cancer cells switch between different adaptive states and evade therapeutic interventions is essential for clinical management. In this study, the in vivo cellular dynamics of a new chronic myeloid leukaemia cell line displaying altered phenotype and resistance to tyrosine kinase inhibitors were investigated in correlation with their parental cells for invasiveness/metastasis, angiogenic potential and population kinetics. We showed that the cells exhibiting drug resistance and plastic phenotype possess an increased capacity for invasion compared to their parental cells, that exposure to imatinib mesylate has the potential to enhance cellular motility and that in a leukaemic cell population, even a minority of plastic cells exhibit improved migratory ability. Furthermore, we show that these plastic cells have angiogenic and extravasation potential. The present study provides significant insights into the cellular dynamics displayed by a TKI-resistant, phenotypically plastic CML cell line, using a zebrafish (Danio rerio) xenograft model.
了解癌细胞在不同适应状态之间切换并逃避治疗干预的机制对于临床管理至关重要。在这项研究中，研究了一种新的慢性髓系白血病细胞系在体内的细胞动力学，该细胞系表现出改变的表型和对酪氨酸激酶抑制剂的耐药性，并与它们的亲本细胞进行了相关性研究，以研究其侵袭/转移、血管生成潜力和群体动力学。我们表明，与亲本细胞相比，表现出耐药性和可塑性表型的细胞具有更高的侵袭能力，暴露于甲磺酸伊马替尼有可能增强细胞迁移能力，并且在白血病细胞群体中，即使是少数可塑性细胞也表现出增强的迁移能力。此外，我们表明这些可塑性细胞具有血管生成和渗出潜力。本研究使用斑马鱼（Danio rerio）异种移植模型，深入了解了一种 TKI 耐药、表型可塑性 CML 细胞系的细胞动力学。
