COMPARISON OF FRTL-5 CELL-GROWTH INVITRO WITH THAT OF XENOTRANSPLANTED CELLS AND THE THYROID OF THE RECIPIENT MOUSE
COMPARISON OF FRTL-5 CELL-GROWTH INVITRO WITH THAT OF XENOTRANSPLANTED CELLS AND THE THYROID OF THE RECIPIENT MOUSE
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DOI：
10.1210/endo-128-1-211
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发表时间：
1991-01-01
期刊：
影响因子：
4.8
通讯作者：
ZAKARIJA, M
中科院分区：
文献类型：
--
作者：
PETER, HJ;GERBER, H;ZAKARIJA, M
本工作旨在利用[~3H]胸腺嘧啶核苷标记，在尽可能相似的条件下比较体外细胞生长动力学和体内生长动力学。为此，FRTL-5细胞被培养成单层和三维球体，嵌入胶原凝胶中，并同时移植到高氯酸盐和低碘饮食处理的裸鼠体内。移植物的生长与宿主小鼠的甲状腺相比，在完整的甲状腺中，[H-3]胸腺嘧啶核苷标记的滤泡细胞(FLC；24-h标记)在甲状腺激素暴露3周后缓慢增加，最高达到10%，随后的自我调节在7周时下降到3%。在6个腺瘤中发现了4倍高的FLC，这表明生长抑制机制的局灶性失效。在非融合单层培养中，FLC高达90%，即使在细胞紧密接触的大型个体集群中也是如此。从移植的单分散细胞生长的固体、高细胞移植物显示平均FLC为20%，这是相同刺激的小鼠甲状腺中FLC的5倍。在胶原包埋的细胞中，形成三维球体的平均FLC从体外1周的70%(体内的40%)下降到体外和体内3周的20%，这表明在这两种条件下都有效地自动调节了过度生长。然而，在同时评估的宿主甲状腺中，这些FLC再次远远高于3%的FLC。我们得出结论，在相似的环境条件下，在宿主小鼠的甲状腺中，以单层和三维球体的形式生长的FRTL-5细胞在类似的环境条件下总是表现出比正常的滤泡上皮更高的增殖率。唯一的例外是融合的单层几乎为零增长，而密集排列的三维移植物仍在密集生长。虽然抑制生长的细胞与细胞之间的相互作用在生长的FRTL-5细胞中也是明显起作用的，但它们不如抑制正常卵泡单层外壳内的甲状腺细胞的复制速度。这些机制的局部失效，使得生长速度与移植的FRTL-5细胞相当，导致正常甲状腺形成腺瘤。这些观察呼吁在将FRTL-5细胞的体外生长研究转移到正常甲状腺中普遍存在的体内条件时要谨慎。
The present work was designed to compare in vitro cell growth kinetics with in vivo growth under conditions as similar as possible using labeling with [3H]thymidine. To this purpose, FRTL-5 cells were cultured as monolayers and as three-dimensional spheroids embedded in collagen gels and transplanted simultaneously into nude mice treated with perchlorate and a low iodine diet. The growth of the transplants was compared to that of the thyroids in host mice.In the intact thyroid, the fraction of [H-3]thymidine-labeled follicular cells (FLC; 24-h labeling) increased sluggishly to a maximum of 10% after 3 weeks of goitrogen exposure, with a subsequent autoregulatory decrease to 3% at 7 weeks. A 4-fold higher FLC was found in six adenomas, indicating focal failure of growth-restraining mechanisms. In nonconfluent monolayer cultures the FLC was as high as 90%, even within large individual clusters where cells are in tight mutual contact. Solid, highly cellular grafts growing from transplanted monodispersed cells showed an average FLC of 20%, which is 5 times higher than the FLC in the identically stimulated mouse thyroid. In collagen-embedded cells, forming three-dimensional spheroids, the mean FLC decreased from 70% at 1 week in vitro (40% in vivo) to 20% at 3 weeks both in vitro and in vivo, suggesting effective autoregulation of excessive growth in both conditions. However, these FLC were again much higher than the 3% FLC in simultaneously assessed host thyroids. The difference remained throughout the 45-day period studied.We conclude that FRTL-5 cells growing as monolayers and as three-dimensional spheroids in vitro or after xenotransplantation in vivo invariably show much higher proliferation rates under comparable environmental conditions than the normal follicular epithelium in the thyroids of host mice. The one exception is the confluent monolayer with near-zero growth, while densely packed three-dimensional transplants still grow intensively. Although growth-retarding cell to cell interactions are also clearly operative in growing FRTL-5 cells, they are less effective than those dampening the replication rate of the thyrocytes within the monolayer hull of normal follicles. A local failure of these mechanisms, allowing growth rates comparable to those of grafted FRTL-5 cells results in adenoma formation in normal thyroids. These observations call for caution in the transfer of in vitro growth studies with FRTL-5 cells to in vivo conditions prevailing in the normal thyroid.