title: Profiling of Nutrient Transporter Expression in Human Stem Cell-Derived Cardiomyocytes Exposed to Tyrosine Kinase Inhibitor Anticancer Drugs Using RBD Ligands.
abstract: We applied a novel profiling approach using receptor binding domain (RBD) ligands to cell surface domains of a panel of nutrient transporters to characterize the impact of a number of tyrosine kinase inhibitor anticancer drugs on human stem cell-derived cardiomyocytes. High-content screening and flow cytometry analysis showed diagnostic changes in nutrient transporter expression correlating with glycolysis and oxidative phosphorylation-based cell metabolism in glucose and galactose media. Cluster analysis of RBD binding signatures of drug-treated cells cultured in glucose medium showed good correlation with sensitization of mitochondrial toxicity in cells undergoing oxidative phosphorylation in galactose medium. These data demonstrate the potential for RBD ligands as profiling tools to improve the clinical predictivity of in vitro cell assays for drug toxicity.
authors.affiliation: GE Healthcare, The Maynard Centre, Forest Farm, Whitchurch, Cardiff, UK.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Li
authors.affiliation: METAFORA Biosystems, Pépinière Genopole Entreprises, Evry, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Cousin
authors.affiliation: GE Healthcare, The Maynard Centre, Forest Farm, Whitchurch, Cardiff, UK.
authors.forename: Hayley
authors.initials: H
authors.lastname: Tinkler
authors.affiliation: METAFORA Biosystems, Pépinière Genopole Entreprises, Evry, France.
authors.forename: Jawida
authors.initials: J
authors.lastname: Touhami
authors.affiliation: METAFORA Biosystems, Pépinière Genopole Entreprises, Evry, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Petit
authors.affiliation: GE Healthcare, The Maynard Centre, Forest Farm, Whitchurch, Cardiff, UK nick.thomas@ge.com.
authors.forename: Nick
authors.initials: N
authors.lastname: Thomas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005434:Flow Cytometry; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D008024:Ligands; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000528:radiation effects*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D000072417:Protein Domains; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; D008024:Ligands; D047428:Protein Kinase Inhibitors; C495677:SLC2A1 protein, human; D011505:Protein-Tyrosine Kinases
keywords: cardiomyocytes; high-content screening; nutrient transporters