Conversion of Hyperpolarized [1- 13 C]Pyruvate in Breast Cancer Cells Depends on Their Malignancy, Metabolic Program and Nutrient Microenvironment

• Published in: Cancers Vol. 14; no. 7; p. 1845
• Main Authors: Grashei, Martin, Biechl, Philipp, Schilling, Franz, Otto, Angela M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.04.2022; MDPI
• Subjects: Breast cancer; Cancer therapies; Carboxylation; Cell culture; Citric acid; Compartmentation; Decarboxylation; Enzymatic activity; Enzymes; Glucose; Glutamine; Glycolysis; Kinases; L-Lactate dehydrogenase; Lactic acid; Lymphoma; Magnetic resonance spectroscopy; Malignancy; Metabolism; Metabolites; Metabolomics; Phenotypes; Pyruvate kinase; Pyruvic acid; Tumor cell lines; Tumor microenvironment; Tumors; Germany; LDH; breast cancer cells; compartmentation; hyperpolarized 13C-pyruvate; TCA-cycle; nutrient deprivation; glycolysis; pyruvate kinase; 13C-glucose metabolomics; Warburg effect
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14071845

Hyperpolarized magnetic resonance spectroscopy (MRS) is a technology for characterizing tumors in vivo based on their metabolic activities. The conversion rates ( ) of hyperpolarized [1- C]pyruvate to [1- C]lactate depend on monocarboxylate transporters (MCT) and lactate dehydrogenase (LDH); these are also indicators of tumor malignancy. An unresolved issue is how glucose and glutamine availability in the tumor microenvironment affects metabolic characteristics of the cancer and how this relates to -values. Two breast cancer cells of different malignancy (MCF-7, MDA-MB-231) were cultured in media containing defined combinations of low glucose (1 mM; 2.5 mM) and glutamine (0.1 mM; 1 mM) and analyzed for pyruvate uptake, intracellular metabolite levels, LDH and pyruvate kinase activities, and C -glucose-derived metabolomics. The results show variability of with the different glucose/glutamine conditions, congruent with glycolytic activity, but not with LDH activity or the Warburg effect; this suggests metabolic compartmentation. Remarkably, -values were almost two-fold higher in MCF-7 than in the more malignant MDA-MB-231 cells, the latter showing a higher flux of C-glucose-derived pyruvate to the TCA-cycle metabolites C -citrate and C -malate, i.e., pyruvate decarboxylation and carboxylation, respectively. Thus, MRS with hyperpolarized [1- C-pyruvate] is sensitive to both the metabolic program and the nutritional state of cancer cells.