Tomayko M M, Triche T J, Reynolds C P
Department of Pediatrics, Children's Hospital of Los Angeles, CA 90027, USA.
Int J Dev Neurosci. 1996 Oct;14(6):771-7. doi: 10.1016/s0736-5748(96)00050-0.
Detection of catecholamine production by neuroblastoma is a useful tumor marker. The majority of neuroblastoma patients have elevated levels of urinary catecholamines and/or their metabolites, and have tumors, which show histochemical evidence of catecholamines using glyoxylic acid-induced catecholamine fluorescence. By contrast, continuous cell lines derived from neuroblastomas lack catecholamine fluorescence in vitro. In this study, we report that 11 out of 12 human neuroblastoma cell lines established from catecholamine-positive tumors displayed histochemical evidence of catecholamines when grown as xenografts in athymic (nude) mice. Catecholamine fluorescence in these xenograft tumors decayed over a 5 day period when the cells were placed into tissue culture. Xenograft tumors of cell lines derived from four catecholamine-negative neuroblastomas or seven primitive neuroectodermal tumors (PNET) did not show catecholamine fluorescence. Ultrastructural comparisons of cell lines in vitro with their corresponding tumors in vivo showed that six of eight cell lines had fewer dense core (neurosecretory) granules in vitro compared to the more readily detectable dense core granules seen in nude mouse tumor tissue. These data indicate that catecholamine synthesis and/or storage in human neuroblastoma cells requires factor(s) not present in the in vivo environment. As neuroblastoma cell lines derived from catecholamine-positive tumors retain the ability to produce and store catecholamines in vivo, such cell lines can be used to identify factors critical to catecholamine production in human neurons.
检测神经母细胞瘤产生的儿茶酚胺是一种有用的肿瘤标志物。大多数神经母细胞瘤患者尿儿茶酚胺和/或其代谢产物水平升高，且肿瘤经乙醛酸诱导的儿茶酚胺荧光显示出儿茶酚胺的组织化学证据。相比之下，源自神经母细胞瘤的连续细胞系在体外缺乏儿茶酚胺荧光。在本研究中，我们报告称，从儿茶酚胺阳性肿瘤建立的12个人类神经母细胞瘤细胞系中有11个在无胸腺（裸）小鼠体内作为异种移植生长时显示出儿茶酚胺的组织化学证据。当将这些异种移植肿瘤细胞置于组织培养中时，儿茶酚胺荧光在5天内衰减。源自4个儿茶酚胺阴性神经母细胞瘤或7个原始神经外胚层肿瘤（PNET）的细胞系的异种移植肿瘤未显示儿茶酚胺荧光。体外细胞系与其在体内相应肿瘤的超微结构比较显示，8个细胞系中有6个在体外的致密核心（神经分泌）颗粒比在裸鼠肿瘤组织中更容易检测到的致密核心颗粒少。这些数据表明，人神经母细胞瘤细胞中儿茶酚胺的合成和/或储存需要体内环境中不存在的因子。由于源自儿茶酚胺阳性肿瘤的神经母细胞瘤细胞系在体内保留了产生和储存儿茶酚胺的能力，因此此类细胞系可用于鉴定对人神经元中儿茶酚胺产生至关重要的因子。
