The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase.
The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase.
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DOI：
10.1038/bjc.1998.289
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发表时间：
1998-06
影响因子：
8.8
通讯作者：
Tannock, I F
中科院分区：
文献类型：
--
作者：
Yamagata, M;Hasuda, K;Stamato, T;Tannock, I F
实体瘤形成具有高浓度乳酸的酸性细胞外环境，并且糖酵解产生的乳酸被认为是肿瘤酸性的主要原因。使用乳酸脱氢酶（LDH）缺陷ras转染的中国仓鼠卵巢细胞的实验已经进行了直接解决的假设，乳酸的生产是负责肿瘤酸化。与亲本细胞相比，变异细胞产生的乳酸量可忽略不计，消耗的葡萄糖量也最少。产乳酸的亲本细胞酸化轻度缓冲培养基，但变异细胞没有。移植到裸鼠体内的亲本细胞和变异细胞来源的肿瘤的细胞外pH值（pHe）平均值分别为7.03 ± 0.03和7.03 ± 0.05，两者均显著低于正常肌肉的细胞外pH值（pHe = 7.43 ± 0.03; P < 0.001）。变异肿瘤中的乳酸浓度（450 +/- 90 microg/g（-1）湿重）远低于亲本肿瘤（1880 +/- 140 microg/g（-1）），与血清中的乳酸浓度（400 +/- 35 microg/g（-1））相似。这些数据显示肿瘤中pH值和乳酸盐含量的平均水平之间不一致;结果支持纽韦尔等人（1993）的结果，并表明通过糖酵解产生乳酸导致培养基酸化，但不是唯一的机制，可能不是实体瘤内酸性环境发展的主要机制。
Solid tumours develop an acidic extracellular environment with high concentration of lactic acid, and lactic acid produced by glycolysis has been assumed to be the major cause of tumour acidity. Experiments using lactate dehydrogenase (LDH)-deficient ras-transfected Chinese hamster ovarian cells have been undertaken to address directly the hypothesis that lactic acid production is responsible for tumour acidification. The variant cells produce negligible quantities of lactic acid and consume minimal amounts of glucose compared with parental cells. Lactate-producing parental cells acidified lightly-buffered medium but variant cells did not. Tumours derived from parental and variant cells implanted into nude mice were found to have mean values of extracellular pH (pHe) of 7.03 +/- 0.03 and 7.03 +/- 0.05, respectively, both of which were significantly lower than that of normal muscle (pHe = 7.43 +/- 0.03; P < 0.001). Lactic acid concentration in variant tumours (450 +/- 90 microg g(-1) wet weight) was much lower than that in parental tumours (1880 +/- 140 microg/g(-1)) and similar to that in serum (400 +/- 35 microg/g(-1)). These data show discordance between mean levels of pHe and lactate content in tumours; the results support those of Newell et al (1993) and suggest that the production of lactic acid via glycolysis causes acidification of culture medium, but is not the only mechanism, and is probably not the major mechanism responsible for the development of an acidic environment within solid tumours.