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

被引:81
作者
Pedersen, MWB
Holm, S
Lund, EL
Hojgaard, L
Kristjansen, PEG
机构
[1] Univ Copenhagen, Expt Oncol Lab, PET, DK-2100 Copenhagen, Denmark
[2] Univ Copenhagen, Natl Univ Hosp, Cyclotron Unit, DK-2100 Copenhagen, Denmark
来源
NEOPLASIA | 2001年 / 3卷 / 01期
关键词
VEGF; GLUT-1; hypoxia; HIF-1; alpha; small-cell lung cancer;
D O I
10.1038/sj.neo.7900133
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 expression 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 subpopulations of the same patient tumor. In spite of their common genomic origin they represent consistently different metabolic and microenvironmental phenotypes as well as treatment sensitivities, There were higher levels of Glut-1 protein in 54B and a correspondingly higher FDG uptake in this tumor line (P<.001). During hypoxia a significant upregulation of in VEGF mRNA, GLUT-1 mRNA, and Glut-1 and -3 protein occurred with a distinctly different time course in the two cell lines. A similar co-upregulation of GLUT and VEGF was seen in hypoxic tumors of both lines. There were no significant changes of HIF-1<alpha> mRNA during hypoxia in either of the cell lines. A more detailed understanding of such correlations between glucose metabolism, angiogenesis, and microenvironmental phenotype of tumors, by positron emission tomography (PET) and molecular techniques might further sophisticate our interpretation of glycolytic predominance in tumors as seen by (18)FFDG PET.
引用
收藏
页码:80 / 87
页数:8
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