Hyperglycemia regulates the glucose-transport system of clonal choriocarcinoma cells in vitro. A potential molecular mechanism contributing to the adjunct effect of glucose in tumor therapy.
Glucose is taken up by tumor cells via sodium-independent facilitated diffusion along a concentration gradient. To examine the regulation of this process by substrate concentration, we investigated the effect of hyperglycemia on the glucose-transport system of choriocarcinoma-derived JAR and JEG-3 cells by culturing them for 24, 48 and 96 hr in medium containing either 5.5 (normoglycemia) or 25 (hyperglycemia) mM D-glucose, respectively. Immunocytochemically, choriocarcinoma cells expressed the high-affinity glucose transporter isoforms GLUT1 and GLUT3. Based on initial uptake measurements using 3-O-[14C]methyl-D-glucose, kinetic parameters were calculated as Km = 15 mM and Vmax = 95 fmol/sec per cell for JAR and Km = 9 mM and Vmax = 64 fmol/sec per cell for JEG-3 cells. In JAR cells cultured under hyperglycemic conditions, uptake rates were significantly increased at 15, 20 and 25 mM exogenous D-glucose concentrations as compared with normoglycemic conditions. This effect was due to an increase in Vmax, whereas Km remained unchanged. Using Northern blotting, GLUT1 mRNA levels were higher but GLUT3 transcripts were reduced upon hyperglycemia. Western blotting revealed elevated GLUT1 and GLUT3 expression under hyperglycemic conditions. Hyperglycemia did not significantly influence the glucose-transport system of JEG-3 cells. We conclude that sustained hyperglycemia stimulates the glucose-transport system of JAR, but not of JEG-3, choriocarcinoma cells in vitro due to changes in GLUT1 and GLUT3 expression levels. We speculate that this mechanism may contribute to the beneficial effects of induced hyperglycemia as an adjuvant in tumor therapy.
Department of Obstetrics and Gynecology, University of Graz, Austria. tom.hahn@kfunigraz.ac.at
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Hahn
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Barth
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Hofmann
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Reich
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Lang
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Desoye
D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000328:Adult; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002453:Cell Cycle; D002822:Choriocarcinoma / Q000378:metabolism* / Q000473:pathology; D002999:Clone Cells; D003470:Culture Media; D005260:Female; D005947:Glucose / Q000494:pharmacology; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006801:Humans; D006943:Hyperglycemia; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D009419:Nerve Tissue Proteins; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D002250:Carbon Radioisotopes; D003470:Culture Media; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; D019325:3-O-Methylglucose; D005947:Glucose