Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties

Valentina Pasquale, Giacomo Ducci, Gloria Campioni, Adria Ventrici, Chiara Assalini, Stefano Busti, Marco Vanoni, Riccardo Vago, Elena Sacco

Research output: Contribution to journalArticlepeer-review

Abstract

Bladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading and tumor progression of RT112 and 5637, two Grade 2 cancer cell lines derived from human bladder, representative of luminal-like and basal-like tumors, respectively. The two cell lines have similar proliferation rates, but only 5637 cells show efficient lateral migration. In contrast, RT112 cells are more prone to form spheroids. RT112 cells produce more ATP by glycolysis and OXPHOS, present overall higher metabolic plasticity and are less sensitive than 5637 to nutritional perturbation of cell proliferation and migration induced by treatment with 2-deoxyglucose and metformin. On the contrary, spheroid formation is less sensitive to metabolic perturbations in 5637 than RT112 cells. The ability of metformin to reduce, although with different efficiency, cell proliferation, sphere formation and migration in both cell lines, suggests that OXPHOS targeting could be an effective strategy to reduce the invasiveness of Grade 2 bladder cancer cells.

Original languageEnglish
JournalCells
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 11 2020

Keywords

  • 2D and 3D cultures
  • bladder cancer
  • cellular bioenergetics
  • energy and redox metabolism
  • fatty acids oxidation
  • glycolysis
  • mitochondrial function
  • Operetta CLS™
  • oxidative stress
  • quantitative imaging
  • Seahorse Extracellular Flux Analyzer

ASJC Scopus subject areas

  • Medicine(all)

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