Iavarone A, Lasorella A, Servidei T, Riccardi R, Mastrangelo R
Division of Pediatric Oncology, Catholic University, Rome, Italy.
Cancer Res. 1993 Jan 15;53(2):304-9.
The mechanisms of the uptake and release of m-iodobenzylguanidine (MIGB) have been studied in 5 neuroblastoma (NB) cell lines and in 4 clonal NB sublines with a homogeneous phenotype. A specific uptake system for MIBG was found in 8 of 9 NB cell lines or subpopulations. The uptake was characterized by temperature dependency, high affinity, saturability, sodium dependency, and imipramine sensitivity. The majority of NB cell lines that possessed a specific uptake system for MIBG were also able to efficiently store the incorporated drug. However, 3 NB cell lines were identified without the ability to retain high levels of MIBG, despite the presence of a specific uptake system. We also report that a clonal subline, SH-EP1, which has a nonneuroblastic phenotype, failed both MIBG uptake and retention. Conversely, the parental cell line, SK-N-SH, and the neuroblastic subline SH-SY5Y possessed both a specific uptake system and the ability to store MIBG. In addition, the induction of neuronal differentiation with retinoic acid increased the velocity of uptake and the storage efficiency for MIBG in the clonal subline SH-SY5Y. We conclude that MIBG uptake and storage should be considered to be frequent but independent neuronal functions of human NB cells.
在5种神经母细胞瘤(NB)细胞系和4种具有同质表型的克隆NB亚系中研究了间碘苄胍(MIGB)的摄取和释放机制。在9种NB细胞系或亚群中的8种中发现了MIBG的特异性摄取系统。摄取的特点是依赖温度、高亲和力、可饱和性、依赖钠和对丙咪嗪敏感。大多数具有MIBG特异性摄取系统的NB细胞系也能够有效地储存摄入的药物。然而,尽管存在特异性摄取系统,但仍鉴定出3种NB细胞系没有保留高水平MIBG的能力。我们还报告说,具有非神经母细胞表型的克隆亚系SH-EP1在MIBG摄取和保留方面均失败。相反,亲代细胞系SK-N-SH和神经母细胞亚系SH-SY5Y既具有特异性摄取系统,又具有储存MIBG的能力。此外,用视黄酸诱导神经元分化可提高克隆亚系SH-SY5Y中MIBG的摄取速度和储存效率。我们得出结论,应将MIBG摄取和储存视为人类NB细胞常见但独立的神经元功能。