Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro

We examined the relationship between F-18-labeled 2-fluro-2-deoxy-D-glucose (FDG) uptake, and expression of glucose transporters (GLUTs) in two human small-cell lung cancer (SCLC) lines CPH 54A and CPH 54B, Changes in the exp ression of GLUTs and vascular endothelial growth factor (VEGF) during 12-, 18-, and 24 hours of severe hypoxia in vivo (xenografts) and in vitro (cell cultures) were recorded for both tumor lines. The two SCLC lines are subpo pulations of the same patient tumor. In spite of their common genomic origi n they represent consistently different metabolic and microenvironmental ph enotypes as well as treatment sensitivities, There were higher levels of Gl ut-1 protein in 54B and a correspondingly higher FDG uptake in this tumor l ine (P<.001). During hypoxia a significant upregulation of in VEGF mRNA, GL UT-1 mRNA, and Glut-1 and -3 protein occurred with a distinctly different t ime course in the two cell lines. A similar co-upregulation of GLUT and VEG F was seen in hypoxic tumors of both lines. There were no significant chang es of HIF-1<alpha> mRNA during hypoxia in either of the cell lines. A more detailed understanding of such correlations between glucose metabolism, ang iogenesis, and microenvironmental phenotype of tumors, by positron emission tomography (PET) and molecular techniques might further sophisticate our i nterpretation of glycolytic predominance in tumors as seen by (18)FFDG PET.