Multipotent differentiation of human neuroblastoma cells

神经脊形成多种组织，包括外周神经元、雪旺细胞、黑素细胞和外胚间充质细胞，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，起源于神经脊组织。因此，神经母细胞瘤细胞有望分化为神经细胞、神经鞘细胞或平滑肌细胞。在本研究中，观察到神经母细胞瘤细胞在造血干细胞中的多向分化。1)向神经细胞的分化：在各种分化诱导剂中，合成的维甲酸(E5166)最能诱导神经分化。维甲酸α和β受体的表达随着维甲酸诱导的神经元分化而增强。2)向平滑肌细胞分化：几个神经母细胞瘤细胞系至少具有神经母细胞(N型)和底物粘附型(S型)细胞的两种形态。因此，我们分析了几种平滑肌细胞标记物，包括α-平滑肌肌动蛋白、结蛋白、高分子钙调蛋白、肌球蛋白重链异构体和钙蛋白。在S细胞中检测到α-平滑肌肌动蛋白、结蛋白和钙蛋白的表达，为S细胞的未成熟细胞表型提供了证据，提示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.