On the relation between size of necrosis and diameter of tumor spheroids
On the relation between size of necrosis and diameter of tumor spheroids
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DOI：
10.1016/0360-3016(95)02065-9
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发表时间：
1996-01-15
影响因子：
7
通讯作者：
MuellerKlieser, W
中科院分区：
文献类型：
--
作者：
Groebe, K;MuellerKlieser, W
目的：在以往对多细胞肿瘤球体的实验研究中，中心坏死体的直径被确定为在球体生长后期测得的存活细胞边缘厚度的两倍。这一过程默许了在整个肿瘤的出现和生长过程中，坏死体的直径与整个球体的直径之间存在线性关系。然而，一些实验研究表明，坏死区并不是随着球体的直径而逐渐增长，而是呈现快速的初始增长。本文对这一现象进行了解释。方法与材料：基于底物耗尽或代谢废物堆积导致坏死形成的假设，建立了球体大小与中心坏死体大小之间的理论关系式。结果：该模型模拟了实验观察到的上述行为，因此，这些实验结果并不能为假设其他关于坏死形成的假说提供任何证据，从而使氧耗率在以前发表的数据的范围内，在所有情况下，与测量数据的逼近都好于相应的线性最小二乘拟合度。结论：至少在某些肿瘤细胞系中，底物的耗尽或废物的积累可以解释坏死的形成，而不需要假设任何额外的机制。此外，本文提出的模型提供了另一种方法来确定底物或代谢废物的周转命运，前提是这种物质的耗尽/积累代表了坏死发展的原因。
Purpose: In many previous experimental studies on multicellular tumor spheroids, the spheroid diameter at which central necrosis develops has been determined to be twice the thickness of the viable cell rim measured at a later stage of spheroid growth, This procedure tacitly assumes that there is a linear relation between the diameter of necrosis and that of the whole spheroid over the entire range of emergence and growth of necrosis, However, some experimental investigations have demonstrated that necroses do not grow gradually with spheroid diameter, but show a rapid initial increase, once a few cells have died, The present article offers an explanation for this phenomenon, which is derived from basic diffusion theory.Methods and Materials: A theoretical relation between sizes of spheroids and of their central necroses is developed, which is based on the assumption that formation of necrosis is caused by depletion of substrates or accumulation of metabolic waste products. In a second part, the theoretical model is fitted to experimental data from the literature, and oxygen consumption rate as a function of spheroid size is determined.Results: It turns out that the model closely mimics the experimentally observed behavior described above, These experimental results, therefore, do not furnish any evidence for assuming other hypotheses of necrosis formation, Resulting O-2 consumption rates are well in the range of previously published data, In all cases, approximations to the measured data are better than the corresponding linear least squares fits.Conclusion: At least in some tumor cell lines, depletion of substrates or accumulation of waste products can explain formation of necrosis without the assumption of any additional mechanisms, Moreover, the model presented in this article offers an alternative way of determining the turnover Fate of a substrate or metabolic waste product provided that depletion/accumulation of this substance represents the cause for necrosis development.