Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration.

Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration.
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通过在生理氧浓度下建立新的急性淋巴细胞白血病细胞系来保留高糖酵解表型。

DOI:
10.1016/j.yexcr.2015.03.024
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发表时间:
2015
影响因子:
3.7
通讯作者:
Reynolds,CPatrick
Reynolds,CPatrick
中科院分区:
医学3区
文献类型:
--
作者:
Sheard,MichaelA;Ghent,MatthewV;Cabral,DanielJ;Lee,JoanneC;Khankaldyyan,Vazgen;Ji,Lingyun;Wu,SamuelQ;Kang,MinH;Sposto,Richard;Asgharzadeh,Shahab;Reynolds,CPatrick

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癌细胞通常表现出糖酵解增加和线粒体氧化磷酸化减少,并且即使在有氧条件下,它们也继续表现出糖酵解的一些升高。然而,目前尚不清楚癌细胞系是否采用与它们所来源的原始癌症相当的高水平糖酵解,即使它们的培养条件改变为生理相关的氧浓度。从三个儿童急性淋巴细胞白血病(ALL)患者,我们建立了三对新的细胞系在大气(20%)和生理(骨髓水平,5%)氧浓度。在20%氧气中建立的细胞系表现出较低的增殖、存活、糖酵解基因表达、葡萄糖消耗和乳酸产生。有趣的是,当建立的细胞培养物从一种氧浓度转换为另一种氧浓度持续8周时,细胞系起始期间使用的氧浓度的影响仅部分可逆。这些观察结果表明,在大气氧浓度下建立的ALL细胞系可以表现出相对较低的糖酵解水平,并且这些水平是半永久性的,这表明从细胞系启动时起可能需要生理氧浓度来保持体内白血病通常表现出的高水平糖酵解。
Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemiasin vivo.
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