Erythropoietin activates cell survival pathways in breast cancer stem-like cells to protect them from chemotherapy

Ruggero De Maria Marchiano, Matilde Todaro, Alice Turdo, Monica Bartucci, Flora Iovino, Rosanna Dattilo, Marco Biffoni, Giorgio Stassi, Giulia Federici, Ann Zeuner

Risultato della ricerca: Contributo in rivistaArticolo in rivista

32 Citazioni (Scopus)


Recombinant erythropoietin (EPO) analogs [erythropoiesis-stimulating agents (ESA)] are clinically used to treat anemia in patients with cancer receiving chemotherapy. After clinical trials reporting increased adverse events and/or reduced survival in ESA-treated patients, concerns have been raised about the potential role of ESAs in promoting tumor progression, possibly through tumor cell stimulation. However, evidence is lacking on the ability of EPO to directly affect cancer stem-like cells, which are thought to be responsible for tumor progression and relapse. We found that breast cancer stem-like cells (BCSC) isolated from patient tumors express the EPO receptor and respond to EPO treatment with increased proliferation and self-renewal. Importantly, EPO stimulation increased BCSC resistance to chemotherapeutic agents and activated cellular pathways responsible for survival and drug resistance. Specifically, the Akt and ERK pathways were activated in BCSC at early time points following EPO treatment, whereas Bcl-xL levels increased at later times. In vivo, EPO administration counteracted the effects of chemotherapeutic agents on BCSC-derived orthotopic tumor xenografts and promoted metastatic progression both in the presence and in the absence of chemotherapy treatment. Altogether, these results indicate that EPO acts directly on BCSC by activating specific survival pathways, resulting in BCSC protection from chemotherapy and enhanced tumor progression. © 2013 American Association for Cancer Research.
Lingua originaleEnglish
pagine (da-a)6393-6400
Numero di pagine8
RivistaCancer Research
Stato di pubblicazionePubblicato - 2013


  • Anemia
  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Blotting, Western
  • Breast Neoplasms
  • Cancer Research
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Erythropoietin
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplastic Stem Cells
  • Oncology
  • Signal Transduction
  • Tumor Cells, Cultured


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