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. Glycolysisassociated 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.

Bioenergetic adaptations in chemo-resistant ovarian cancer cells

“…We observed a significant positive correlation between ROS levels and glycolysis. An interesting observation in a few publications is that the ovarian cell lines with high glycolysis also showed high OXPHOS and associated gene expression, indicating that most of the ovarian cancer cell lines favor a highly metabolic phenotype 26,41 . Recently, ovarian cancer cell migration was shown to be fueled by pyruvate, implicating mitochondrial activity in the metastatic process 19 .…”

Assessment of the frequency of mitochondrial tRNA variants in patients with ovarian cancer

“…OC cells, similar to other solid tumour cells and in contrast to normal cells, heavily relied on aerobic glycolysis for energy production, a phenomenon known as the Warburg effect [4]. This effect, which was manifested by increased glucose consumption, decreased oxidative phosphorylation (OXPHOS) and accompanying lactate production, had been confirmed and was generally accepted as it had been demonstrated in various tumours.…”

Urinary interleukin-1ß levels among gynecological patients

“…Increased metabolic activity and glucose concentrations driven by the Warburg effect [45] are associated with highly aggressive OC cell lines [46]. In cancer, the Warburg effect is regarded as a characteristic metabolic process that may contribute to cell survival in a stressful environment, such as the stress of chronic inflammation [47].…”