Abstract
Epidermal growth factor (EGF) has an in vitro inhibitory effect on tumor cells which exhibit a high number of EGF receptors (EGFR). Studies were performed in order to delineate the effects of EGF on glucose metabolism of MDA-468 human breast cancer cells, which have a large number of EGFR. Glucose consumption and lactate production were found to be substantially increased in MDA-468 cells following EGF exposure, while no such effects were detected in MCF-7 breast cancer cells, which have a very low number of EGFR. When glucose levels in the growth medium were increased, the toxicity of EGF was diminished. The energetic status of MDA-468 cells perfused with growth medium containing EGF was monitored by 31P magnetic resonance spectroscopy, and no signs of compromised metabolic state or viability were noted for up to 36 h. The rate of glucose transport and phosphorylation was quantitated by 13C magnetic resonance spectroscopy, utilizing [6-13C]2-deoxyglucose, and a 97% increase was found in MDA-468 cells following EGF administration. The profound effects of EGF on glucose metabolism in cells with very high numbers of EGFR and the lack of toxicity in the perfused system may indicate that the growth-inhibitory effect is confined to the in vitro cultured cells.
Highlights
EnnisP, of Health, Bethesda, Epidermal growth factor (EGF) has an in vitro inhibitory effect on tumor cells which exhibit a high number of EGF receptors (EGFR)
Studies were performed in order to delineate the effects of EGF on glucose metabolism of MDA-468 human breast cancer cells, which have a large number of EGFR
The rate of glucose transport and phosphorylation was quantitated by 13C magnetic resonance spectroscopy, utilizing [6-‘3C]2-deoxyglucose, and a 97% increase was found in MDA-468 cells following EGF administration
Summary
Materials-For cell cultures, “improved” minimal Eagle’s medium (National Institutes of Health Media Center, “regular” IMEM contains 11 mM glucose) was used. Twenty-four h later, medium samples were withdrawn again, and all cells were harvested and counted This method was used because preliminary experiments showed that in the first few days after plating, cell numbers are too small to detect changes in glucose concentrations accurately. Peak heights were multiplied by this ratio, and the normalized integral values obtained corresponded to the metabolite concentrations This method was found to be more appropriate than simple integration because significant base line variations rendered integrals alone inaccurate, MRS data acquisition and processing were performed with identical parameters throughout all experiments, and measurements with external reference (methylphosphonic acid) showed that quantitative. Protein assays were performed and MRS data were normalized for studvina the effects of EGF on the ohosohorvlation rates of 2-DG and comparing between MDA-468 and MCF-7-cells. Statistical analyses were performed with the paired, double-tailed, Student’s t test (p < 0.05)
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