title: Metabolic alterations during the growth of tumour spheroids.
abstract: Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms.
authors.affiliation: Doctoral Training Centre, University of Oxford, Rex Richards Building, Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bloch
authors.forename: Hannah
authors.initials: H
authors.lastname: Smith
authors.forename: Victoria
authors.initials: V
authors.lastname: van Hamel Parsons
authors.forename: David
authors.initials: D
authors.lastname: Gavaghan
authors.forename: Catherine
authors.initials: C
authors.lastname: Kelly
authors.forename: Alexander
authors.initials: A
authors.lastname: Fletcher
authors.forename: Philip
authors.initials: P
authors.lastname: Maini
authors.forename: Richard
authors.initials: R
authors.lastname: Callaghan
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010427:Pentose Phosphate Pathway; D018874:Spheroids, Cellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D005947:Glucose