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).
Methods: 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.
Results: 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.
Conclusion: 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.