Journal of Bioenergetics and Biomembranes

, Volume 42, Issue 1, pp 55–67 | Cite as

Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia

  • Katarína Smolková
  • Nadège Bellance
  • Francesca Scandurra
  • Elisabeth Génot
  • Erich Gnaiger
  • Lydie Plecitá-Hlavatá
  • Petr Ježek
  • Rodrigue Rossignol
Article

Abstract

Breast cancer cells can survive and proliferate under harsh conditions of nutrient deprivation, including limited oxygen and glucose availability. We hypothesized that such environments trigger metabolic adaptations of mitochondria, which promote tumor progression. Here, we mimicked aglycemia and hypoxia in vitro and compared the mitochondrial and cellular bioenergetic adaptations of human breast cancer (HTB-126) and non-cancer (HTB-125) cells that originate from breast tissue. Using high-resolution respirometry and western blot analyses, we demonstrated that 4 days of glucose deprivation elevated oxidative phosphorylation five-fold, increased the spread of the mitochondrial network without changing its shape, and decreased the apparent affinity of oxygen in cancer cells (increase in C50), whereas it remained unchanged in control cells. The substrate control ratios also remained constant following adaptation. We also observed the Crabtree effect, specifically in HTB-126 cells. Likewise, sustained hypoxia (1% oxygen during 6 days) improved cell respiration in non-cancer cells grown in glucose or glucose-deprived medium (+ 32% and +38%, respectively). Conversely, under these conditions of limited oxygen or a combination of oxygen and glucose deprivation for 6 days, routine respiration was strongly reduced in cancer cells (−36% in glucose medium, −24% in glucose-deprived medium). The data demonstrate that cancer cells behave differently than normal cells when adapting their bioenergetics to microenvironmental conditions. The differences in hypoxia and aglycemia tolerance between breast cancer cells and non-cancer cells may be important when optimizing strategies for the treatment of breast cancer.

Keywords

Mitochondria Oxidative phosphorylation Breast cancer Tumor bioenergetics Hypoxia Respirometry 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Katarína Smolková
    • 1
    • 2
    • 6
  • Nadège Bellance
    • 1
    • 2
  • Francesca Scandurra
    • 3
  • Elisabeth Génot
    • 4
  • Erich Gnaiger
    • 5
  • Lydie Plecitá-Hlavatá
    • 6
  • Petr Ježek
    • 6
  • Rodrigue Rossignol
    • 1
    • 2
  1. 1.INSERM U688BordeauxFrance
  2. 2.Université Victor Segalen Bordeaux 2BordeauxFrance
  3. 3.OROBOROS INSTRUMENTSInnsbruckAustria
  4. 4.INSERM U889, IECBPessacFrance
  5. 5.Department of General and Transplant Surgery, D. Swarovski Research LaboratoryMedical University of InnsbruckInnsbruckAustria
  6. 6.Institute of Physiology, Dept. 75Academy of Sciences of the Czech RepublicPragueCzech Republic

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