Scatena 2017 Abstract MITOEAGLE Barcelona

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COST Action MITOEAGLE
Mitochondria and cancer stem cells in hepatocarcinoma. An illustrative example of a tangled methodological approach.

Link: MitoEAGLE

Bottoni P, Pieroni L, Urbani A, Scatena R (2017)

Event: MitoEAGLE Barcelona 2017

COST Action MITOEAGLE

Recent data confirm that PPAR-ligands, like metformin, may cause erosion of cancer stem cells (CSCs), also called tumor initiating cells (TICs) or stem like cancer cells in vivo and in vitro [1]. Intriguingly, this effect seems to depend on a derangement of mitochondrial respiratory chain, specifically at level of complex I [2]. CSC play a pivotal role in cancer initiation, metastasis and recurrence, as well as in resistance to therapy [3]. On the other side, deep metabolic characterization of these tumorigenic cells revealed a strict dependency on mitochondrial respiration versus glycolysis, suggesting the existence of a common metabolic program active in these slow cycling cancer cells across different tumors. In facts, when OXPHOS activity is suppressed, these cancer cells change their behavior and phenotype showing a dramatic reduction in tumorigenic potential. Hence, the study of the molecular interrelationships among iatrogenic complex I derangement and CSC targeting must become a focus of contemporary research, not only from a therapeutic point of view, but also for a fundamental advance of the molecular biology of cancer in general.

By high-resolution respirometry (HRR) we tried to better characterize the mitochondrial derangement induced by these drugs. HRR results were compared with data obtained by other well know methodological approaches.

This comparison stresses that a real translational cancer research urgently needs correct methodological bioenergetic approach requiring a careful evaluation of mitochondrial respiratory pathophysiology. The adoption of protocols, technologies and standard procedures really accurate, appropriate, sensitive and above all specific is becoming mandatory. The advantages and disadvantages with isolated mitochondria and intact cells approaches in hepatocarcinoma could be an illustrative example.


Bioblast editor: Kandolf G O2k-Network Lab: IT Rome Scatena R


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 


Tissue;cell: Liver  Preparation: Intact cells, Isolated mitochondria  Enzyme: Complex I 


HRR: Oxygraph-2k  Event: A1 


Affiliations

Bottoni P(1), Pieroni L(2), Urbani A(1), Scatena R(1)
  1. Inst Biochem Clinical Biochem, Catholic Univ
  2. Proteomics Metabonomics Lab, CERC-S.Lucia Foundation; Rome, Italy

References

  1. Prost S, Relouzat F, Spentchian M, Ouzegdouh Y, Saliba J, Massonnet G, Beressi JP, Verhoeyen E, Raggueneau V, Maneglier B, Castaigne S, Chomienne C, Chrétien S, Rousselot P, Leboulch P (2015) Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature 525:380-3.
  2. Pernicova I, Korbonits M (2014) Metformin-mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol 10:143-56.
  3. Scatena R, Mordente A, Giardina B (2011) Advances in Cancer Stem Cell Biology. NEW YORK: Springer Science.