Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells.
Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells.
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DOI：
10.1002/cncr.25868
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发表时间：
2011-07-01
期刊：
影响因子：
6.2
通讯作者：
Myers, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Sandulache, Vlad C.;Ow, Thomas J.;Pickering, Curtis R.;Frederick, Mitchell J.;Zhou, Ge;Fokt, Izabela;Davis-Malesevich, Melinda;Priebe, Waldemar;Myers, Jeffrey N.
肿瘤代谢是疾病进展和治疗反应的重要因素。了解头颈部鳞状细胞癌（HNSCC）的代谢表型，将有助于为这种肿瘤类型制定适当的抗代谢策略。测定一组15个HNSCC细胞系的葡萄糖和谷氨酰胺依赖性以及对代谢抑制剂的敏感性。此外，使用质谱法/液相色谱法的广谱代谢组学分析与还原电位、三磷酸腺苷（ATP）和乳酸产生的个体测量相结合，以表征细胞代谢表型。HNSCC能量和还原电位水平密切反映了细胞外葡萄糖浓度。葡萄糖饥饿诱导细胞死亡，尽管激活二级能量途径。相反，谷氨酰胺不是HNSCC生存所必需的，也不是重要的能量来源。2-脱氧葡萄糖（2-DG）及其氟代衍生物降低HNSCC细胞的糖酵解和Krebs循环活性、细胞能量和还原电位，抑制细胞增殖。添加二甲双胍可增强2-DG的作用，但不能抑制戊糖磷酸途径或二甲双胍分解。尽管依赖于葡萄糖催化剂，我们确定了一个子集的细胞系相对耐饥饿。对一个这样的细胞系（HN 30）的探索表明，野生型p53的存在可以部分保护肿瘤细胞免受葡萄糖饥饿。HNSCC肿瘤细胞依赖于葡萄糖而不是谷氨酰胺来产生能量和存活，这为靶向葡萄糖代谢的治疗策略提供了理论基础。然而，抗代谢策略可能需要根据肿瘤背景，更具体地说，p53状态进行调整。
Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow development of appropriate anti-metabolic strategies for this tumor type. A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. Additionally, broad-spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate (ATP) and lactate production to characterize cellular metabolic phenotypes. HNSCC energy and reducing potential levels closely mirrored extra-cellular glucose concentrations. Glucose starvation induced cell death despite activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2-deoxyglucose (2-DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy and reducing potential and inhibited HNSCC cell proliferation. 2-DG effects were potentiated by the addition of metformin, but not inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, we identified a subset of cell lines relatively resistant to starvation. Exploration of one such cell line (HN30) suggests that the presence of wild-type p53 can partially protect tumor cells from glucose starvation. HNSCC tumor cells are dependent on glucose, not glutamine for energy production and survival, providing a rationale for treatment strategies targeting glucose catabolism. However, anti-metabolic strategies may need to be tailored to the tumor background, more specifically, p53 status.
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DOI：
10.1016/s0360-3016(01)01630-3
发表时间：
2001-10-01
影响因子：
7
作者：
Brizel, DM;Schroeder, T;Mueller-Klieser, W
通讯作者：
Mueller-Klieser, W
影响因子：
4.8
作者：
Osthus, RC;Shim, H;Dang, CV
通讯作者：
Dang, CV
影响因子：
4.8
作者：
McFate, Thomas;Mohyeldin, Ahmed;Verma, Ajay
通讯作者：
Verma, Ajay
影响因子：
5.7
作者：
Kurtoglu, Metin;Gao, Ningguo;Lampidis, Theodore J.
通讯作者：
Lampidis, Theodore J.
影响因子：
5.5
作者：
Hamel, P.;Abed, E.;Moreau, R.
通讯作者：
Moreau, R.