Reske S N, Grillenberger K G, Glatting G, Port M, Hildebrandt M, Gansauge F, Beger H G
Department of Nuclear Medicine, University of Ulm, Germany.
J Nucl Med. 1997 Sep;38(9):1344-8.
Increased glycolysis is a characteristic metabolic feature of a malignant transformed phenotype. In cultured cells transformed by viruses or activated oncogenes, enhanced glycolytic metabolism is mediated by the overexpression of glucose transporter 1 (Glut-1) and key regulatory glycolytic enzymes. Whether increased glucose metabolism in solid human malignant tumors is related to the overexpression of key regulatory proteins of glucose metabolism is presently unknown. We thus studied the expression of Glut-1 and glucose uptake, assessed with 2-fluorodeoxyglucose (FDG) and PET in human pancreatic carcinoma (PC) and chronic mass-forming pancreatitis (MFP).
Glucose uptake was measured in the fasting state with FDG and PET in 12 patients with PC and 15 patients with MFP. The standardized uptake value (SUV) of FDG was determined as a global quantitative measure of tissue glucose utilization in cancer tissue or MFP. The expression of Glut-1 and Glut-4 was analyzed from operatively removed cancer or MFP tissue by Northern analysis or semiquantitative reverse transcriptase-polymerase chain reaction. The count ratio of Glut-1 to Glut-4 transcripts was used as an indicator of selective Glut-1 up-regulation.
The SUVs of FDG in patients with cancer and MFP were 2.98 +/- 1.23 and 1.25 +/- 0.51 (p < 0.01), respectively. Northern analysis showed intense Glut-1 expression in four of five patients with cancer but not in any of the five patients with MFP that were tested. In PC, Glut-1 and Glut-4 transcripts were found in five of five and three of 10 patients, respectively, using reverse transcriptase-polymerase chain reaction, whereas in MFP, Glut-1 was detected in one of five and Glut-4 was detected in all five patients. The Glut-1-to-Glut-4 transcript ratios were 6.17 +/- 1.27 in patients with cancer and 0.42 +/- 0.12 in patients with MFP. The mean Glut-1 concentration in eight patients with cancer was 1.71 nmol of Glut-1 mRNA/microg of mRNA (range, 0.0446-9.43) and 0.15 (range, 0-1.55) (p < 0.05) in 13 patients with MFP.
The concomitant enhancement of glucose utilization and selective overexpression of Glut-1 mRNA in pancreatic cancer but not in MFP suggested constitutive activation of Glut-1 gene or decreased degradation of Glut-1 mRNA in human pancreatic cancer. These findings may imply a potential for the early detection of pancreatic cancer with FDG and PET and identify new targets for anticancer therapy.
糖酵解增加是恶性转化表型的一个特征性代谢特征。在病毒转化或激活的癌基因转化的培养细胞中，糖酵解代谢增强是由葡萄糖转运蛋白1（Glut-1）和关键调节糖酵解酶的过表达介导的。目前尚不清楚人类实体恶性肿瘤中葡萄糖代谢增加是否与葡萄糖代谢关键调节蛋白的过表达有关。因此，我们研究了Glut-1的表达以及葡萄糖摄取情况，采用2-氟脱氧葡萄糖（FDG）和PET对人胰腺癌（PC）和慢性肿块形成性胰腺炎（MFP）进行评估。
在12例PC患者和15例MFP患者中，使用FDG和PET在空腹状态下测量葡萄糖摄取。FDG的标准化摄取值（SUV）被确定为癌症组织或MFP中组织葡萄糖利用的整体定量指标。通过Northern分析或半定量逆转录聚合酶链反应，对手术切除的癌症或MFP组织中Glut-1和Glut-4的表达进行分析。Glut-1与Glut-4转录本的计数比用作Glut-1选择性上调的指标。
癌症患者和MFP患者的FDG的SUV分别为2.98±1.23和1.25±0.51（p<0.01）。Northern分析显示，在接受检测的5例癌症患者中有4例Glut-1表达强烈，而5例MFP患者中无一例表达强烈。在PC中，使用逆转录聚合酶链反应分别在5例患者中的5例和10例患者中的3例中发现了Glut-1和Glut-4转录本，而在MFP中，5例患者中有1例检测到Glut-1，所有5例患者中均检测到Glut-4。癌症患者的Glut-1与Glut-4转录本比率为6.17±1.27，MFP患者为0.42±0.12。8例癌症患者的平均Glut-1浓度为1.71 nmol Glut-1 mRNA/μg mRNA（范围为0.0446 - 9.43），13例MFP患者为0.15（范围为0 - 1.55）（p<0.05）。
胰腺癌中葡萄糖利用的同时增强和Glut-1 mRNA的选择性过表达，而MFP中未出现这种情况，提示人胰腺癌中Glut-1基因的组成性激活或Glut-1 mRNA降解减少。这些发现可能意味着FDG和PET在胰腺癌早期检测方面具有潜力，并为抗癌治疗确定新的靶点。
