Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Sweden.
Cancer Rep (Hoboken). 2023 Jun;6(6):e1819. doi: 10.1002/cnr2.1819. Epub 2023 Apr 25.
Most children with Wilms tumour are successfully treated with multidrug chemotherapy and surgery. These treatments cause severe side effects for the patients, an issue that needs to be addressed by exploring other treatment options with less or no side effects. One option is to complement current therapies with agents that could potentially induce tumour cell differentiation, for example retinoic acid (RA).
To facilitate quick assessment of an agent's effect on Wilms tumour differentiation by a rapid in vitro model system.
Here WiT49 and CCG99-11 Wilms tumour cells were treated with 10 μM RA for 72 h or 9 days. Cultured cells were scraped off from Petri dishes, pelleted and embedded in paraffin in the same way as clinical tumour specimens are preserved. Cell morphology and differentiation were evaluated by analyses of haematoxylin eosin (H&E) and immunohistochemical stainings. Based on H&E, WT1 and CKAE1/3 stainings, RA treatment induced further epithelial differentiation of WiT49 cells, whereas there was no sign of induced maturation in CCG99-11 cells. Ki67 staining showed that RA inhibited cell proliferation in both cell lines.
Our study shows that in vitro culturing of WiT49 and CCG99-11 cells, followed by pelleting and paraffin embedding of cell pellets, could aid in a quick evaluation of potential differentiating agents against Wilms tumour. In addition, our results strengthen previous results that retinoic acid could be a potential complement to regular Wilms tumour treatment.
大多数患有肾母细胞瘤的儿童通过多药物化疗和手术成功治疗。这些治疗会给患者带来严重的副作用,需要通过探索其他副作用较小或没有的治疗方案来解决这个问题。一种选择是用可能诱导肿瘤细胞分化的药物来补充当前的治疗方法,例如视黄酸(RA)。
通过快速的体外模型系统,促进对药物对肾母细胞瘤分化的作用的快速评估。
在这里,WiT49 和 CCG99-11 肾母细胞瘤细胞用 10 μM RA 处理 72 小时或 9 天。培养的细胞从培养皿中刮下,离心并以与临床肿瘤标本保存相同的方式包埋在石蜡中。通过对苏木精-伊红(H&E)和免疫组织化学染色的分析来评估细胞形态和分化。基于 H&E、WT1 和 CKAE1/3 染色,RA 处理诱导 WiT49 细胞进一步上皮分化,而 CCG99-11 细胞没有诱导成熟的迹象。Ki67 染色显示 RA 抑制了两种细胞系的细胞增殖。
我们的研究表明,WiT49 和 CCG99-11 细胞的体外培养,随后对细胞沉淀进行离心和石蜡包埋,有助于快速评估潜在的针对肾母细胞瘤的分化剂。此外,我们的结果加强了先前的结果,即视黄酸可能是常规肾母细胞瘤治疗的潜在补充。