3D in vitro test system for vestibular schwannoma
3D in vitro test system for vestibular schwannoma
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DOI：
10.1016/j.jneumeth.2020.108633
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发表时间：
2020-04-15
影响因子：
3
通讯作者：
Hagemann, Carsten
中科院分区：
文献类型：
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作者：
Breun, Maria;Martellotta, Donato Daniel;Hagemann, Carsten
前庭神经鞘瘤是第八脑神经的良性肿瘤，由雪旺细胞增殖引起(Louis等人，2016)。前庭神经鞘瘤的触发因素是Merlin蛋白功能的丧失。Merlin是一种连接细胞膜和细胞骨架的FERM(4.1蛋白质/Ezrin/Radixin/moesin)蛋白质。它通过细胞间黏附和与细胞外基质的黏附而激活(Cooper和Gianotti，2014)。在2型神经纤维瘤病患者中，22号染色体上Merlin的一个等位基因在出生时就有缺陷，在一生中第二次点击可能会导致蛋白质功能的完全丧失。这些患者在年轻时出现双侧前庭神经鞘瘤，此外还有其他几种肿瘤，如脑膜瘤和室管膜瘤(Hanemann，2008；Hui-Su Lim等人，2014)。目前确定的前庭神经鞘瘤的治疗方案有手术、放射外科手术或“观察和等待”方法。然而，在神经纤维瘤病患者中，由于肿瘤的数量、侵袭性和生长速度的原因，这些治疗可能性的适用性是有限的。因此，迫切需要系统的治疗方法(Hanemann，2008)。此前，CXCR4已被证明是治疗前庭神经鞘瘤的潜在新靶点，因为它在这些肿瘤中过表达(Breun等人，2018)。然而，目前的治疗策略主要是使用二维(2D)细胞培养系统开发的，通常只有一个已建立的细胞系。然而，这样的测试系统并不能真正反映体内的生理条件，这就是为什么新开发的疗法在临床试验中经常失败，尽管在2D细胞培养中取得了令人振奋的结果。
Vestibular schwannomas are benign tumors of the eighth cranial nerve caused by Schwann cell proliferation (Louis et al., 2016). The trigger of vestibular schwannoma is loss of the merlin protein function. Merlin is a FERM (4.1 protein/ezrin/radixin/moesin) protein that links the cell membrane and the cytoskeleton. It is activated by intercellular adhesion and by attachment to the extracellular matrix (Cooper and Gianotti, 2014). In patients with neurofibromatosis type 2, one allele for merlin on chromosome 22 is defective at birth, and a second hit during life time may result in complete loss of protein function. These patients develop bilateral vestibular schwannoma at a young age, in addition to several other tumors, such as meningioma and ependymoma (Hanemann, 2008; Hui-Su Lim et al., 2014). The currently established therapeutic options for vestibular schwannoma are surgery, radiosurgery or the “watch & wait” approach. However, in patients with neurofibromatosis, the applicability of these therapeutic possibilities is limited, due to the high number of tumors, their invasiveness and rate of growth. Therefore, systemic therapeutic approaches are urgently needed (Hanemann, 2008).Previously, CXCR4 has been demonstrated to be a potential new therapeutic target in the treatment of vestibular schwannoma, since it is overexpressed in these tumors (Breun et al., 2018). However, current therapeutic strategies are predominantly developed using two-dimensional (2D) cell culture systems, often with only a single established cell line. However, such test systems do not really reflect the physiological conditions in vivo, which is why newly developed therapeutics often fail in clinical trials, despite promising results in 2D cell culture.