VARIATIONS IN TUMOR-CELL GROWTH-RATES AND METABOLISM WITH OXYGEN CONCENTRATION, GLUCOSE-CONCENTRATION, AND EXTRACELLULAR PH
VARIATIONS IN TUMOR-CELL GROWTH-RATES AND METABOLISM WITH OXYGEN CONCENTRATION, GLUCOSE-CONCENTRATION, AND EXTRACELLULAR PH
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DOI：
10.1002/jcp.1041510220
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发表时间：
1992-05-01
影响因子：
5.6
通讯作者：
SUTHERLAND, RM
中科院分区：
文献类型：
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作者：
CASCIARI, JJ;SOTIRCHOS, SV;SUTHERLAND, RM
肿瘤和多细胞肿瘤球状体在生长时可形成氧浓度、葡萄糖浓度和细胞外pH的梯度。 为了计算这些梯度并评估其对肿瘤生长的影响，有必要量化这些变量对肿瘤细胞代谢和生长的影响。 在这项工作中，在各种氧浓度、葡萄糖浓度和细胞外pH水平下测量EMT 6/Ro小鼠乳腺肿瘤细胞的氧消耗速率、葡萄糖消耗速率和生长速率。 在胞外pH为7.25时，随着葡萄糖浓度从5.5 mM降低到0.4 mM，EMT 6/Ro细胞的耗氧速率增加了近2倍。然而，葡萄糖浓度对耗氧速率的影响在胞外pH为6.95时很轻微，在胞外pH为6.60时完全消失。 当氧浓度从0.21 mM降低到0.023 mM时，EMT 6/Ro细胞的葡萄糖消耗速率增加了大约40%，当细胞外pH从7.25降低到6.95时，EMT 6/Ro细胞的葡萄糖消耗速率降低了大约60%。 EMT 6/Ro细胞的生长速率随着氧浓度和细胞外pH的降低而降低;然而，需要严格的条件来停止细胞生长（0.0082 mM氧和6.60的细胞外pH）。 从这些数据发展经验相关性以表达EMT 6/Ro细胞生长速率、氧消耗速率和葡萄糖消耗速率，作为氧浓度、葡萄糖浓度和细胞外pH的函数。这些经验相关性使得有可能对氧浓度、葡萄糖浓度和细胞外pH的梯度进行数学建模。和胞外pH值的EMT 6/Ro多细胞球体的扩散/反应方程的解决方案。 诸如此类的计算，沿着EMT 6/Ro多细胞球体中的氧和pH微电极测量，表明球体内部区域的营养物浓度和pH水平足够低以引起营养物消耗速率和细胞生长速率的显著变化。 然而，在观察到静止细胞的EMT 6/Ro球状体中测量或计算的pH和氧浓度不足以导致细胞生长停止，表明观察到的静止一定是由于酸性pH、氧消耗或葡萄糖消耗以外的因素。
Tumors and multicellular tumor spheroids can develop gradients in oxygen concentration, glucose concentration, and extracellular pH as they grow. In order to calculate these gradients and assess their impact on tumor growth, it is necessary to quantify the effect of these variables on tumor cell metabolism and growth. In this work, the oxygen consumption rates, glucose consumption rates, and growth rates of EMT6/Ro mouse mammary tumor cells were measured at a variety of oxygen concentrations, glucose concentrations, and extracellular pH levels. At an extracellular pH of 7.25, the oxygen consumption rate of EMT6/Ro cells increased by nearly a factor of 2 as the glucose concentration was decreased from 5.5 mM to 0.4 mM. This effect of glucose concentration on oxygen consumption rate, however, was slight at an extracellular pH of 6.95 and disappeared completely at an extracellular pH of 6.60. The glucose consumption rate of EMT6/Ro cells increased by roughly 40% when the oxygen concentration was reduced from 0.21 mM to 0.023 mM and decreased by roughly 60% when the extracellular pH was decreased from 7.25 to 6.95. The growth rate of EMT6/Ro cells decreased with decreasing oxygen concentration and extracellular pH; however, severe conditions were required to stop cell growth (0.0082 mM oxygen and an extracellular pH of 6.60). Empirical correlations were developed from these data to express EMT6/Ro cell growth rates, oxygen consumption rates, and glucose consumption rates, as functions of oxygen concentration, glucose concentration, and extracellular pH. These empirical correlations make it possible to mathematically model the gradients in oxygen concentration, glucose concentration, and extracellular pH in EMT6/Ro multicellular spheroids by solution of the diffusion/reaction equations. Computations such as these, along with oxygen and pH microelectrode measurements in EMT6/Ro multicellular spheroids, indicated that nutrient concentration and pH levels in the inner regions of spheroids were low enough to cause significant changes in nutrient consumption rates and cell growth rates. However, pH and oxygen concentrations measured or calculated in EMT6/Ro spheroids where quiescent cells have been observed were not low enough to cause the cessation of cell growth, indicating that the observed quiescence must have been due to factors other than acidic pH, oxygen depletion, or glucose depletion.