Dataset Information

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes.

ABSTRACT: BACKGROUND:Both hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism-related markers were examined in stage I - resectable stage IIIA non-small cell lung cancer (NSCLC). Furthermore, expression of metabolism-related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism. METHODS:Mutation analysis was performed for 97 tumors. Glucose and glutamine metabolism-related marker expression was measured by immunofluorescent staining (protein) and qPCR (mRNA) (n = 81). RESULTS:Glutamine metabolism-related markers were significantly higher in adeno- than squamous cell NSCLCs. Glucose transporter 1 (GLUT1) protein expression was higher in solid compared to lepidic adenocarcinomas (P?

SUBMITTER: Meijer TWH

PROVIDER: S-EPMC6885430 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes.

Meijer Tineke W H TWH Looijen-Salamon Monika G MG Lok Jasper J van den Heuvel Michel M Tops Bastiaan B Tops Bastiaan B Kaanders Johannes H A M JHAM Span Paul N PN Bussink Johan J

Thoracic cancer 20191030 12

<h4>Background</h4>Both hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism-related markers were examined in stage I - resectable stage IIIA non-small cell lung cancer (NSCLC). Furthermore, expression of metabolism-related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism.<h4>Methods</h4>Mutation analysis was performed for 97 tumors. Glucose and glutamine metabolism-related marker expre ...[more]

PMID: 31668020

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Project description:Energy metabolism in proliferating cultured rat thymocytes was compared with that of freshly prepared non-proliferating resting cells. Cultured rat thymocytes enter a proliferative cycle after stimulation by concanavalin A and Lymphocult T (interleukin-2), with maximal rates of DNA synthesis at 60 h. Compared with incubated resting thymocytes, glucose metabolism by incubated proliferating thymocytes was 53-fold increased; 90% of the amount of glucose utilized was converted into lactate, whereas resting cells metabolized only 56% to lactate. However, the latter oxidized 27% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and aldolase in proliferating thymocytes were increased 12-, 17-, 30- and 24-fold respectively, whereas the rate of pyruvate oxidation was enhanced only 3-fold. The relatively low capacity of pyruvate degradation in proliferating thymocytes might be the reason for almost complete conversion of glucose into lactate by these cells. Glutamine utilization by rat thymocytes was 8-fold increased during proliferation. The major end products of glutamine metabolism are glutamate, aspartate, CO2 and ammonia. A complete recovery of glutamine carbon and nitrogen in the products was obtained. The amount of glutamate formed by phosphate-dependent glutaminase which entered the citric acid cycle was enhanced 5-fold in the proliferating cells: 76% was converted into 2-oxoglutarate by aspartate aminotransferase, present in high activity, and the remaining 24% by glutamate dehydrogenase. With resting cells the same percentages were obtained (75 and 25). Maximal activities of glutaminase, glutamate dehydrogenase and aspartate aminotransferase were increased 3-, 12- and 6-fold respectively in proliferating cells; 32% of the glutamate metabolized in the citric acid cycle was recovered in CO2 and 61% in aspartate. In resting cells this proportion was 41% and 59% and in mitogen-stimulated cells 39% and 65% respectively. Addition of glucose (4 mM) or malate (2 mM) strongly decreased the rates of glutamine utilization and glutamate conversion into 2-oxoglutarate by proliferating thymocytes and also affected the pathways of further glutamate metabolism. Addition of 2 mM-pyruvate did not alter the rate of glutamine utilization by proliferating thymocytes, but decreased the rate of metabolism beyond the stage of glutamate significantly. Formation of acetyl-CoA in the presence of pyruvate might explain the relatively enhanced oxidation of glutamate to CO2 (56%) by proliferating thymocytes.

Dataset Information

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes.

Publications

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes.

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