Elevated TrkA receptor expression is associated with all-trans retinoic acid-induced neuroblastoma differentiation
Elevated TrkA receptor expression is associated with all-trans retinoic acid-induced neuroblastoma differentiation
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DOI：
10.4238/2015.october.26.15
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发表时间：
2015-01-01
影响因子：
0.4
通讯作者：
Zhang, H. Y.
中科院分区：
文献类型：
--
作者：
Gao, Q.;Chen, C. F.;Zhang, H. Y.
神经母细胞瘤是儿童肿瘤中最常见且最致命的肿瘤之一。然而，一部分患有神经母细胞瘤的婴儿表现出自发消退。自发消退的机制仍有待阐明。 TrkA 在神经元的分化和功能中发挥着重要作用；丰富的 TrkA 表达与神经母细胞瘤的良好预后相关。全反式维甲酸（ATRA）是治疗急性早幼粒细胞白血病（APL）的一线药物，已被证明可以诱导分化并抑制细胞生长。收集我院住院患者的神经母细胞瘤组织，进行原代细胞培养，分离纯化细胞系。台盼蓝拒染法计数活细胞数，相差显微镜下观察形态变化。 RT-PCR用于测定TrkA的表达水平。本研究成功建立了人神经母细胞瘤细胞系；此外，我们证明 ATRA 会诱导生长停滞并促进神经母细胞瘤细胞的分化。此外，ATRA 还可显着提高 TrkA mRNA 的表达水平。因此，我们得出结论，TrkA 受体表达升高与 ATRA 诱导的神经母细胞瘤细胞生长停滞和分化有关。本研究结果为分化诱导ATRA治疗神经母细胞瘤的临床应用提供理论依据。
Neuroblastoma is the most common and one of the deadliest among pediatric tumors; however, a subset of infants with neuroblastoma display spontaneous regression. The mechanism of spontaneous regression remains to be elucidated. TrkA plays an essential role in the differentiation and functionality of neurons; abundant TrkA expression is associated with favorable prognosis of neuroblastoma. All-trans retinoic acid (ATRA), a first-line drug for acute promyelocytic leukemia (APL) treatment, has been shown to induce differentiation and inhibit cell growth. Neuroblastoma tissues in our hospital inpatient were collected, primary cell culture was performed, and the cells were separated and purified to be cell line. Trypan blue exclusion was used to count the numbers of cells alive, morphological changes were observed under the phase-contrast microscope. RT-PCR was used to determine the expression level of TrkA. In this study, a human neuroblastoma cell line was successfully established; in addition, we demonstrated that ATRA induces growth arrest and promotes the differentiation of neuroblastoma cells. In addition, ATRA was shown to significantly increase the levels of TrkA mRNA expression. Therefore, we concluded that the elevated expression of the TrkA receptor is associated with ATRA-induced growth arrest and differentiation of neuroblastoma cells. The results of this study provide a theoretical basis for the clinical application of differentiation-inducing ATRA for neuroblastoma therapy.