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Multipotent differentiation of human neuroblastoma cells

人神经母细胞瘤细胞的多能分化

基本信息

批准号：
04670613
负责人：
SUGIMOTO Tohru
金额：
$ 1.34万
依托单位：
Miyazaki Medical College (1993)Kyoto Prefectural University of Medicine (1992)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

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.

神经嵴产生多种组织，包括外周神经元、许旺细胞、黑素细胞和外胚间充质细胞，其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，起源于神经嵴组织。本研究观察了造血干细胞中神经母细胞瘤细胞的多向分化潜能。1）向神经元细胞的分化：在各种分化诱导剂中，合成类维生素A（E5166）最能诱导神经元分化。α和β维甲酸受体的表达随着维甲酸诱导的神经元分化而增强。2）向平滑肌细胞的分化：几种神经母细胞瘤细胞系具有至少两种形态学外观，即神经母细胞（N型）和基质细胞（S型）细胞。因此，分析了几种平滑肌细胞标志物，包括α-平滑肌肌动蛋白、结蛋白、高分子量钙调蛋白、肌球蛋白重链亚型和钙调蛋白。在S型细胞中检测到α-平滑肌肌动蛋白、结蛋白和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，提示神经母细胞瘤细胞向平滑肌细胞分化的可能途径。