人类神经母细胞瘤细胞分化过程中生化与形态学变化的综合评估

A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation.

作者信息

Lanciotti M, Montaldo P G, Folghera S, Lucarelli E, Cornaglia-Ferraris P, Ponzoni M

机构信息

Pediatric Oncology Research Laboratory, G. Gaslini Children's Hospital, Genoa, Italy.

出版信息

Cell Mol Neurobiol. 1992 Jun;12(3):225-40. doi: 10.1007/BF00712928.

DOI:10.1007/BF00712928

PMID:1358448

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11567463/

Abstract

The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.

摘要

研究了视黄酸、γ-干扰素、阿糖胞苷、神经生长因子、肿瘤坏死因子和12-O-十四酰佛波醇-13-乙酸酯对人神经母细胞瘤细胞系LAN-5的影响。诱导后评估了乙酰胆碱酯酶、神经元特异性烯醇化酶、儿茶酚胺及相关神经递质、血管活性肠肽和P物质的细胞内水平。2. 视黄酸、γ-干扰素、阿糖胞苷和12-O-十四酰佛波醇-13-乙酸酯对细胞形态有强烈影响。视黄酸和γ-干扰素的主要作用是使细胞簇松散并使长神经突延长；阿糖胞苷诱导细胞体肿胀并显著促进神经突形成。用12-O-十四酰佛波醇-13-乙酸酯处理后，细胞变得小而圆且有神经突。相反，神经生长因子和肿瘤坏死因子引起的改变较轻微。视黄酸、γ-干扰素、阿糖胞苷和12-O-十四酰佛波醇-13-乙酸酯降低了细胞增殖率，而神经生长因子和肿瘤坏死因子则无此作用。3. 视黄酸和γ-干扰素显著刺激了乙酰胆碱酯酶活性。除12-O-十四酰佛波醇-13-乙酸酯外，所有处理对神经元特异性烯醇化酶活性均无影响，12-O-十四酰佛波醇-13-乙酸酯使其活性提高了1.6倍。4. 视黄酸和γ-干扰素降低了细胞内儿茶酚胺及相关代谢产物的含量，而阿糖胞苷，尤其是12-O-十四酰佛波醇-13-乙酸酯对其细胞内积累具有刺激活性。5. 最后，γ-干扰素显著提高了细胞相关血管活性肠肽水平，视黄酸、阿糖胞苷和12-O-十四酰佛波醇-13-乙酸酯在较小程度上也有此作用。6. 得出结论，与LAN-5细胞分化相关的最相关生化变化涉及神经递质和神经肽的种类。这些事件在质量和数量上有所不同，可能是由于每种诱导剂在决定神经元表型多样性时触发的基因表达模式复杂所致。