The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism
The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism
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DOI：
10.1016/j.yexcr.2015.04.007
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发表时间：
2015-07-01
影响因子：
3.7
通讯作者：
Silva, Branca M.
中科院分区：
文献类型：
--
作者：
Conde, Vanessa R.;Oliveira, Pedro E.;Silva, Branca M.
癌细胞呈现出特定的代谢行为。我们推测膀胱癌的进展可能伴随着细胞糖酵解谱的变化。我们研究了两种人膀胱癌细胞，RT4和TCC40，其中后者代表了更具侵袭性的阶段。通过质子核磁共振测量细胞外培养基中葡萄糖、丙酮酸、丙氨酸和乳酸的水平。测定葡萄糖转运蛋白1（GLUT 1）和3（GLUT 3）、单羧酸转运蛋白4（MCT 4）、磷酸果糖激酶1（PFK 1）、谷丙转氨酶（GPT）和乳酸脱氢酶（LDH）的蛋白表达水平。我们的数据表明，葡萄糖消耗和GLUT3水平在两种细胞系中是相似的，但TCCI2细胞显示较低水平的GLUT1和PFK表达。与较高水平的乳酸和丙氨酸生产一致的丙酮酸消耗的增加，也在TCCI3细胞中检测到。此外，TCCB1细胞呈现较低的GPT和LDH蛋白表达水平。这些结果表明，膀胱癌进展与细胞糖酵解谱的改变有关，即在更积极的阶段从葡萄糖消耗转变为丙酮酸消耗。这可能有助于开发新的治疗方法，并确定癌症进展的生物标志物。(C)2015 Elsevier Inc. All rights reserved.
Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. (C) 2015 Elsevier Inc. All rights reserved.