Multipotent differentiation of human neuroblastoma cells

神经嵴产生多种组织，包括周围神经元、雪旺细胞、黑素细胞和外胚间质细胞，其中包括大动脉的平滑肌细胞。神经母细胞瘤是儿童常见的恶性实体瘤之一，起源于神经嵴的组织。因此，神经母细胞瘤细胞可以分化为神经元细胞、神经鞘细胞或平滑肌细胞。本研究对造血干细胞中神经母细胞瘤细胞的多能分化进行了研究。1)向神经元细胞分化：在多种分化诱导剂中，人工合成类视黄醇（E5166）最能诱导神经元分化。α和β视黄酸受体的表达随着类视黄酸诱导的神经元分化而增强。2)向平滑肌细胞分化：几种神经母细胞瘤细胞系至少具有神经母细胞（n型）和底物粘附（s型）细胞两种形态。因此，我们分析了几种平滑肌细胞标志物，包括-平滑肌肌动蛋白、聚乳酸蛋白、高分子量聚乳酸蛋白、肌球蛋白重链异构体和钙钙蛋白。在s型细胞中检测α -平滑肌肌动蛋白、desmin和calponin蛋白和/或mRNA。这些结果提供了s型细胞未成熟平滑肌细胞表型的证据，提示了神经母细胞瘤细胞向平滑肌细胞分化的可能途径。

The neural crest gives rise to a variety tissues, including peripheral neurons, Schwann cells, melanocytes and ectomesencymal cells, which include the smooth muscle cells of large arteries. Neuroblastoma, one of the common malignant solid tumors in childhood, arises from tissues derived from the neural crest. Therefore neroblastoma cells could be expected to differetiate into either neuronal, schwannian, or smooth muscle cells.In this study multipotent differentiation of neuroblastoma cells, observed in hematopoetic stem cells, was investigated.1) Differentiation into neuronal cells : Neuronal differentiation could be most induced by the synthetic retinoid (E5166) among various differentiation inducers. The expression of both alpha and beta retinoic acid receptors was augmented with retinoid-induced neuronal differentiation.2) Differentiation into smooth muscle cells : Several neuroblastoma cell lines have at least two morphological appearances of neuroblastic (N-type) and substrate-adhesiveness (S-type) cells. Therefore several smooth muscle cell markers, including alpha-smooth muscle actin, desmin, high molecular weight caldesmon, myosin heavy chain isoforms and calponin, were analyzed. In S-type cells, alpha-smooth muscle actin, desmin and calponin protein and/or mRNA were detected.These results provide the evidence of immature smooth muscle cell phenotype of S-type cells, indicating the possible differentiation pathway of neuroblastoma cells into smooth muscle cells.