title: Protein profiles in human ovarian cancer cell lines correspond to their metabolic activity and to metabolic profiles of respective tumor xenografts.
abstract: Many solid tumors show a large variability in glycolytic activity and lactate accumulation, which has been correlated with different metastatic spread, radioresistance and patient survival. To investigate potential differences in protein profiles underlying these metabolic variances, the highly glycolytic human ovarian cancer cell line OC316 was investigated and compared with the less glycolytic line IGROV-1. Extracellular acidification and oxygen consumption were analyzed with an extracellular flux analyzer. Glycolysis-associated proteins, including specific membrane transporters, were quantified through in-cell western analyses. Metabolic properties of corresponding tumor xenografts were assessed via induced metabolic bioluminescence imaging. Extracellular flux analyses revealed elevated bioenergetics of OC316 cells. Hexokinase II, pyruvate kinase, pyruvate dehydrogenase E1 beta subunit and pyruvate dehydrogenase kinase 1, as well as the glucose transporter 1 and the monocarboxylate transporter 4, were overexpressed in these cells compared with IGROV-1. When generating tumor xenografts in SCID mice, cells maintained their glycolytic behavior, i.e. OC316 showed higher lactate concentrations than IGROV-1 tumors. In summary, a congruency between protein profiles and metabolic properties has been demonstrated in the human ovarian cancer lines investigated. Also, a perpetuation of glycolytic characteristics during the transition from in vitro to the in vivo situation has been documented. This model system could be useful for systematic studies on therapeutic intervention by manipulation of tumor glycolysis and associated pathways.
authors.affiliation: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.  
authors.forename: Christian
authors.initials: C
authors.lastname: Fabian
authors.forename: Lisa
authors.initials: L
authors.lastname: Koetz
authors.forename: Elena
authors.initials: E
authors.lastname: Favaro
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mueller-Klieser
authors.forename: Ulrike G A
authors.initials: UG
authors.lastname: Sattler
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006019:Glycolysis; D006801:Humans; D055442:Metabolome; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010101:Oxygen Consumption; D011506:Proteins / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins