TY - JOUR

T1 - Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro

AU - Pedersen, M W

AU - Holm, S

AU - Lund, E L

AU - Højgaard, L

AU - Kristjansen, P E

PY - 2001/4/28

Y1 - 2001/4/28

N2 - We examined the relationship between (18)F- 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-1alpha 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 18FFDG PET.

AB - We examined the relationship between (18)F- 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-1alpha 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 18FFDG PET.

KW - Animals

KW - Anoxia

KW - Blotting, Western

KW - Carcinoma, Small Cell

KW - DNA-Binding Proteins

KW - Endothelial Growth Factors

KW - Fluorodeoxyglucose F18

KW - Glucose

KW - Glucose Transporter Type 1

KW - Humans

KW - Hypoxia-Inducible Factor 1

KW - Hypoxia-Inducible Factor 1, alpha Subunit

KW - In Vitro Techniques

KW - Lung Neoplasms

KW - Lymphokines

KW - Male

KW - Mice

KW - Mice, Nude

KW - Monosaccharide Transport Proteins

KW - Nuclear Proteins

KW - RNA, Messenger

KW - Tomography, Emission-Computed

KW - Transcription Factors

KW - Tumor Cells, Cultured

KW - Up-Regulation

KW - Vascular Endothelial Growth Factor A

KW - Vascular Endothelial Growth Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/sj/neo/7900133

DO - 10.1038/sj/neo/7900133

M3 - Journal article

C2 - 11326319

VL - 3

SP - 80

EP - 87

JO - Neoplasia

JF - Neoplasia

SN - 1522-8002

IS - 1

ER -