Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK.
European Xenopus Resource Centre, School of Biological Sciences, University of Portsmouth, Portsmouth, PO1 2DY, UK.
Gene Expr Patterns. 2021 Jun;40:119183. doi: 10.1016/j.gep.2021.119183. Epub 2021 May 19.
Neuroblastoma is a neural crest-derived paediatric cancer that is the most common and deadly solid extracranial tumour of childhood. It arises when neural crest cells fail to follow their differentiation program to give rise to cells of the sympathoadrenal lineage. These undifferentiated cells can proliferate and migrate, forming tumours mostly found associated with the adrenal glands. Activating mutations in the kinase domain of anaplastic lymphoma kinase (ALK) are linked to high-risk cases, where extensive therapy is ineffective. However, the role of ALK in embryonic development, downstream signal transduction and in metastatic transformation of the neural crest is poorly understood. Here, we demonstrate high conservation of the ALK protein sequences among vertebrates. We then examine alk mRNA expression in the frog models Xenopus laevis and Xenopus tropicalis. Using in situ hybridisation of Xenopus embryos, we show that alk is expressed in neural crest domains throughout development, suggesting a possible role in neuroblastoma initiation. Lastly, RT-qPCR analyses show high levels of alk expression at tadpole stages. Collectively, these data may begin to elucidate how alk functions in neural crest cells and how its deregulation can result in tumorigenesis.
神经母细胞瘤是一种源自神经嵴的小儿癌症,是儿童期最常见和最致命的颅外实体肿瘤。当神经嵴细胞未能遵循其分化程序,产生交感肾上腺谱系的细胞时,就会发生这种肿瘤。这些未分化的细胞可以增殖和迁移,形成主要与肾上腺相关的肿瘤。间变性淋巴瘤激酶(ALK)激酶结构域的激活突变与高危病例有关,这些病例的广泛治疗无效。然而,ALK 在胚胎发育、下游信号转导以及神经嵴的转移转化中的作用还知之甚少。在这里,我们证明了 ALK 蛋白序列在脊椎动物中的高度保守性。然后,我们检查了青蛙模型非洲爪蟾和爪蟾中的 alk mRNA 表达。通过对非洲爪蟾胚胎的原位杂交,我们表明 alk 在整个发育过程中都在神经嵴区域表达,这表明它在神经母细胞瘤的发生中可能发挥作用。最后,RT-qPCR 分析显示,在蝌蚪阶段 alk 的表达水平很高。综上所述,这些数据可能开始阐明 alk 在神经嵴细胞中的作用以及其失调如何导致肿瘤发生。