BIOLOGICAL RESPONSE OF MULTICELLULAR EMT6 SPHEROIDS TO EXOGENOUS LACTATE
BIOLOGICAL RESPONSE OF MULTICELLULAR EMT6 SPHEROIDS TO EXOGENOUS LACTATE
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DOI：
10.1002/ijc.2910470528
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发表时间：
1991-03-12
影响因子：
6.4
通讯作者：
MUELLERKLIESER, W
中科院分区：
文献类型：
--
作者：
BOURRATFLOECK, B;GROEBE, K;MUELLERKLIESER, W
采用多细胞球体模型研究了在肿瘤微区发现的乳酸浓度升高对细胞生长、活力和代谢状态的影响。EMT6/Ro细胞的球体在37℃、5%或20% （v/v）氧气条件下培养，使用含有不同浓度外源乳酸的搅拌培养基，从0.0 mM（标准条件）到20.0 mM。外源乳酸浓度的升高导致生长饱和时最大球体直径显著减小，例如，在20% O2条件下，在0.0和20.0 mM乳酸中，球体直径分别从1700 mu-m到700 mu-m。组织学研究表明，在氧气浓度为20%时，乳酸浓度升高会增加活细胞边缘的厚度，而在氧气浓度为5%时，这种相关性则相反。通过标准酶法测定，在乳酸浓度增加的情况下，球体的培养与代谢途径的转变有关，在20%和5%的氧气条件下，从净生产到乳酸利用率的增加。无论外部氧浓度如何，在高乳酸浓度（9.0和20.0 mM）培养的球体中，用微电极测量的氧张力（PO2）值比在标准条件下低。这一发现反映了细胞氧消耗随着外部乳酸水平升高而大幅增加。在给定的乳酸浓度下，根据理论考虑，由测量的PO2分布得出的呼吸速率在5% O2下明显低于20% O2下。
The influence of elevated lactate concentrations, as found in tumor microregions, on cellular growth, viability, and metabolic state was studied employing the multicellular spheroid model. Spheroids of EMT6/Ro cells were cultured at 37-degrees-C in 5% or 20% (v/v) oxygen, using stirred media with various concentrations of exogenous lactate ranging from 0.0 mM (standard conditions) to 20.0 mM. Elevated concentrations of exogenous lactate led to a considerable decrease of the maximum spheroid diameter at growth saturation, e.g., for 20% O2 from around 1700-mu-m to 700-mu-m in 0.0 and 20.0 mM lactate respectively. Histological investigations showed that the thickness of the viable cell rim was increased by elevated lactate concentrations in 20% O2, whereas this correlation was reversed in 5% O2. Cultivation of spheroids in increasing lactate concentrations was associated with a shift of metabolic pathways from net production to increased utilization of lactate in both 20% and 5% O2, as determined by standard enzymatic assays. Oxygen tension (PO2) values measured with micro-electrodes were less in spheroids cultured in high lactate (9.0 and 20.0 mM) than under standard conditions, irrespective of the external oxygen concentration. This finding reflected a substantial increase in the cellular O2 consumption with elevated external lactate levels. At given lactate concentrations, respiration rates that were derived from measured PO2 distributions by theoretical considerations were significantly lower in 5% O2 than in 20% O2.