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人神经母细胞瘤细胞系IGR-N-835建立过程中表型和基因型特征的稳定性

Stability of phenotypic and genotypic traits during the establishment of a human neuroblastoma cell line, IGR-N-835.

作者信息

Bettan-Renaud L, Bayle C, Teyssier J R, Benard J

机构信息

Laboratoire de Pharmacologie Clinique et Moléculaire, Institut Gustave Roussy, 94800 Villejuif, France.

出版信息

Int J Cancer. 1989 Sep 15;44(3):460-6. doi: 10.1002/ijc.2910440314.

Abstract

A prerequisite for the study of biological characteristics in neuroblastoma is the establishment of cell lines from tumors of patients. For our study a neuroblastoma cell line, IGR-N-835, was established from a primary tumor. During in vitro establishment of this line morphological changes were observed. IGR-N-835 exhibited both anchored cells and floating clusters. When cultured on bovine endothelial corneal cellular matrix, all tumor cells anchored to the matrix and proliferated, giving a continuous cell line. IGR-N-835 was studied in vitro and in vivo. Treatment with retinoic acid resulted in cell growth arrest and morphological differentiation. IGR-N-835 was highly tumorigenic in nude mice, exhibited a doubling time of 65 hr and was able to form colonies in methyl-cellulose with a cloning efficiency of 0.46%. Immunocytochemical studies showed reactivity of this line and its primary passages with CE7 monoclonal antibody (MAb). Cytogenetic analyses revealed stable mode and markers resulting from structural changes in chromosomes 10, 11 and 21 with no homogeneously staining regions or double minute chromosomes. Genomic amplification and overexpression of the N-myc oncogene exhibited by the patient's tumor remained unchanged in nude mouse xenografts and the IGR-N-835 cell line. These phenotypic and genotypic traits were unchanged during establishment of this neuroblastoma line. IGR-N-835 could therefore constitute a suitable material for the study of the biology or therapeutics of human neuroblastoma.

摘要

研究神经母细胞瘤生物学特性的一个前提条件是从患者肿瘤中建立细胞系。在我们的研究中,从一例原发性肿瘤中建立了神经母细胞瘤细胞系IGR-N-835。在该细胞系的体外建立过程中,观察到了形态学变化。IGR-N-835既有贴壁细胞,也有悬浮细胞团。当在牛角膜内皮细胞基质上培养时,所有肿瘤细胞均贴附于基质并增殖,形成了一个连续的细胞系。对IGR-N-835进行了体外和体内研究。用维甲酸处理导致细胞生长停滞和形态分化。IGR-N-835在裸鼠中具有高度致瘤性,倍增时间为65小时,能够在甲基纤维素中形成集落,克隆效率为0.46%。免疫细胞化学研究显示该细胞系及其原代传代细胞与CE7单克隆抗体(MAb)有反应性。细胞遗传学分析揭示了稳定的模式和由10号、11号和21号染色体结构变化导致的标记,没有均匀染色区或双微体染色体。患者肿瘤所表现出的N-myc癌基因的基因组扩增和过表达在裸鼠异种移植物和IGR-N-835细胞系中保持不变。在该神经母细胞瘤细胞系的建立过程中,这些表型和基因型特征未发生改变。因此,IGR-N-835可构成研究人类神经母细胞瘤生物学或治疗学的合适材料。

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