Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. It arises during development of the sympathetic nervous system. Netrin-4 (NTN4), a laminin-related protein, has been proposed as a key factor to target NB metastasis, although there is controversy about its function. Here, we show that NTN4 is broadly expressed in tumor, stroma and blood vessels of NB patient samples. Furthermore, NTN4 was shown to act as a cell adhesion molecule required for the migration induced by Neogenin-1 (NEO1) in SK-N-SH neuroblastoma cells. Therefore, we propose that NTN4, by forming a ternary complex with Laminin γ1 (LMγ1) and NEO1, acts as an essential extracellular matrix component, which induces the migration of SK-N-SH cells.

中文翻译：

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Netrin-4 /层粘连蛋白γ1/ Neogenin-1复合物介导SK-N-SH神经母细胞瘤细胞的迁移。

神经母细胞瘤（NB）是最常见的小儿颅外实体瘤。它在交感神经系统发育期间出现。Netrin-4（NTN4）是一种层粘连蛋白相关蛋白，尽管它的功能尚存在争议，但已被认为是靶向NB转移的关键因素。在这里，我们显示NTN4在NB患者样品的肿瘤，基质和血管中广泛表达。此外，NTN4被显示为SK-N-SH神经母细胞瘤细胞中Neogenin-1（NEO1）诱导的迁移所需的细胞粘附分子。因此，我们建议NTN4通过与层粘连蛋白γ1（LMγ1）和NEO1形成三元复合物，作为必需的细胞外基质成分，从而诱导SK-N-SH细胞的迁移。