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膀胱癌从低侵袭阶段进展到高侵袭阶段与葡萄糖和丙酮酸代谢的严重改变有关。

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism.

作者信息

Conde Vanessa R, Oliveira Pedro F, Nunes Ana R, Rocha Cátia S, Ramalhosa Elsa, Pereira José A, Alves Marco G, Silva Branca M

机构信息

CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.

CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP, Portugal.

出版信息

Exp Cell Res. 2015 Jul 1;335(1):91-8. doi: 10.1016/j.yexcr.2015.04.007. Epub 2015 Apr 20.

DOI:10.1016/j.yexcr.2015.04.007
PMID:25907297
Abstract

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.

摘要

癌细胞呈现出一种特殊的代谢行为。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TCCSUP,其中后者代表更具侵袭性的阶段。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。测定了葡萄糖转运蛋白1(GLUT1)和3(GLUT3)、单羧酸转运蛋白4(MCT4)、磷酸果糖激酶-1(PFK1)、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,两种细胞系中的葡萄糖消耗和GLUT3水平相似,但TCCSUP细胞中GLUT1和PFK的表达水平较低。在TCCSUP细胞中还检测到丙酮酸消耗增加,这与较高水平的乳酸和丙氨酸产生相一致。此外,TCCSUP细胞中GPT和LDH的蛋白表达水平较低。这些结果表明,膀胱癌的进展与细胞糖酵解谱的改变有关,即在更具侵袭性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识别癌症进展的生物标志物。

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