Yeger H, Baumal R, Pawlin G, Tonin P, Nissen L, Kaplinsky C, Phillips M J
Department of Pathology, Hospital for Sick Children, Toronto, Ontario.
Differentiation. 1988 Dec;39(3):216-27. doi: 10.1111/j.1432-0436.1988.tb00095.x.
Two new neuroblastoma (NB) cell lines, NUB-6 and NUB-7, were established from recurrent and primary NB tumours respectively and identified conclusively as NB by their phenotypic characteristics, catecholamine production and N-myc amplification. The cell lines could be distinguished on the bases of distinctive growth patterns in monolayer culture and semi-solid media (collagen gel and agarose), neurite formation and their response to four classes of growth and differentiation modulators. The NUB-6 cell line consisted of two distinct cell subtypes, small typical neuroblasts and larger spheroid-forming cells, while NUB-7 was homogeneously neuroblastic. Class-I agents (dibutyrl cyclic AMP [dbcAMP], butyrate, and papaverine) inhibited growth of both cell lines, while only dbcAMP stimulated the formation of short neurites by NUB-6 neuroblast cells in monolayer culture and collagen. Of the class-II agents (vitamins), retinoic acid inhibited growth of both cell lines and stimulated formation of long neurites by NUB-6 cells and NUB-7 cells in later passages. In contrast, vitamin E inhibited growth of NUB-6 and late-passage NUB-7, but stimulated early passage NUB-7. The class III agent (nerve growth factor) resembled vitamin E. The class-IV agents (interferons; rIFN-alpha 2a and rIFN-gamma 1) inhibited growth of both cell lines in monolayer culture and agarose, but stimulated NUB-6 neuroblasts and early passage NUB-7 cells to form long neurites. Thus phenotypically distinct NB cell lines were established in vitro and shown to be differentially influenced by various growth and differentiation modulators. The potent effect of IFN suggests a role for these modulators in NB behaviour in vivo.
两种新的神经母细胞瘤（NB）细胞系，NUB - 6和NUB - 7，分别从复发性和原发性NB肿瘤中建立，并通过其表型特征、儿茶酚胺产生和N - myc扩增最终鉴定为NB。这些细胞系可根据单层培养和半固体培养基（胶原凝胶和琼脂糖）中的独特生长模式、神经突形成以及它们对四类生长和分化调节剂的反应来区分。NUB - 6细胞系由两种不同的细胞亚型组成，即小的典型神经母细胞和较大的形成球状体的细胞，而NUB - 7是均匀的神经母细胞型。I类试剂（二丁酰环磷腺苷[dbcAMP]、丁酸盐和罂粟碱）抑制两种细胞系的生长，而只有dbcAMP在单层培养和胶原中刺激NUB - 6神经母细胞形成短神经突。在II类试剂（维生素）中，视黄酸抑制两种细胞系的生长，并在后期传代时刺激NUB - 6细胞和NUB - 7细胞形成长神经突。相比之下，维生素E抑制NUB - 6和后期传代的NUB - 7的生长，但刺激早期传代的NUB - 7。III类试剂（神经生长因子）与维生素E相似。IV类试剂（干扰素；rIFN - α2a和rIFN - γ1）在单层培养和琼脂糖中抑制两种细胞系的生长，但刺激NUB - 6神经母细胞和早期传代的NUB - 7细胞形成长神经突。因此，在体外建立了表型不同的NB细胞系，并显示它们受到各种生长和分化调节剂的不同影响。干扰素的强效作用表明这些调节剂在体内NB行为中起作用。
