B cell lymphoma with different metabolic characteristics show distinct sensitivities to metabolic inhibitors
B cell lymphoma with different metabolic characteristics show distinct sensitivities to metabolic inhibitors
复制标题
具有不同代谢特征的B细胞淋巴瘤对代谢抑制剂表现出不同的敏感性。
DOI：
10.7150/jca.24331
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Yang, Wenbiao
中科院分区：
文献类型：
--
作者：
Liu, Xiaoxia;Wang, Li;Yang, Wenbiao
目的：癌细胞的代谢发生了深刻的变化(葡萄糖和谷氨酰胺代谢异常)。靶向肿瘤代谢是一种很有前途的治疗策略。淋巴瘤可以分为许多不同的类型，而且非常复杂。因此，本研究旨在了解不同代谢特性的B细胞淋巴瘤细胞对代谢抑制剂是否具有不同的敏感性。方法：根据对谷氨酰胺和葡萄糖的依赖程度，将9株B细胞淋巴瘤细胞分为不同的代谢亚型。然后检测OCR、ECAR、葡萄糖消耗和乳酸生成、线粒体含量和生长率。结果：根据对谷氨酰胺和葡萄糖的依赖程度，我们成功地将B细胞淋巴瘤细胞株分为三种不同的代谢亚型，其中一种亚型定义为谷氨酰胺和葡萄糖等利用亚型(Gln=Glu)，另两种亚型为Gln成瘾和Glu依赖亚型。这三个亚型在葡萄糖和谷氨酰胺的利用、糖酵解和线粒体功能以及增殖率方面存在显著差异。谷氨酰胺依赖亚型和谷氨酰胺依赖亚型在细胞对谷氨酰胺和糖酵解代谢抑制剂的敏感性上也存在差异。结论：细胞对葡萄糖/谷氨酰胺依赖程度越高，对葡萄糖/谷氨酰胺耗竭或糖酵解/谷氨酰胺分解抑制的敏感性越强，对谷氨酰胺/糖酵解/糖酵解抑制剂的敏感性降低。根据代谢特点靶向肿瘤代谢，可能为B细胞淋巴瘤的治疗提供新的治疗策略。
Purpose: Cancer cells exhibit profound alterations in their metabolism (abnormal glucose and glutamine metabolism). Targeting cancer metabolism is a promising therapeutic strategy. Lymphoma can be classified into many different types and it is very complicated. Therefore, in this paper, we want to know whether the B cell lymphoma cells with different metabolic characteristics have distinct sensitivities to metabolic inhibitors.Methods: We classified 9 B cell lymphoma cell lines into different metabolic subtypes according to the dependency on glutamine and glucose. Then we detected the OCR, ECAR, glucose consumption and lactate production, mitochondrial content and growth rate. And we also determined the IC50 of these 9 cell lines to metabolic inhibitors.Results: According to the dependency on glutamine and glucose, we successfully classified three distinct metabolic subtypes in B cell lymphoma cell lines, one subtype was defined glutamine and glucose equally utilized subtype (GLN=Glu), whereas the other two subtypes were GLN-addicted and Glu-dependent. And these three subtypes showed striking differences in glucose and glutamine utilization, glycolysis and mitochondrial function, and proliferation rate. GLN-addicted and Glu-dependence subtypes also showed differences in cell sensitivity to inhibitors of glutamine and glycolysis metabolism, respectively. However, GLN=Glu subtype seems minimal sensitive to glycolytic and glutaminolytic inhibitors, and with high proliferation rate.Conclusions: The cells rely more on glucose/gltamine have a stronger sensitivity to glucose/glutamine depletion or glycolysis/glutaminolysis inhibition and a lessened sensitivity to glutaminolysis/glycolysis inhibitors. To target tumor metabolism based on metabolic characteristics may provide a new therapeutic strategy for the treatment of B cell lymphoma.