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Erythropoietin activates cell survival pathways in breast cancer stem-like cells to protect them from chemotherapy
- Publication Year :
- 2013
- Publisher :
- American Association for Cancer Research, 2013.
-
Abstract
- 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. Cancer Res; 73(21); 6393–400. ©2013 AACR.
- Subjects :
- MAPK/ERK pathway
Oncology
Cancer Research
medicine.medical_treatment
Fluorescent Antibody Technique
Apoptosis
Mice, SCID
Immunoenzyme Techniques
Mice
Cell Movement
Mice, Inbred NOD
hemic and lymphatic diseases
Tumor Cells, Cultured
Cultured
Blotting
Anemia
Flow Cytometry
Tumor Cells
TRIALS
Disease Progression
Neoplastic Stem Cells
Female
Western
Signal Transduction
medicine.drug
STIMULATING AGENTS
EXPRESSION
medicine.medical_specialty
Blotting, Western
Antineoplastic Agents
Breast Neoplasms
SCID
RECOMBINANT-HUMAN-ERYTHROPOIETIN, STIMULATING AGENTS, EXPRESSION, MORTALITY, TRIALS, ANEMIA, ALPHA, ALDH1
Breast cancer
In vivo
Internal medicine
medicine
Animals
Humans
Breast cancer, Cancer stem cells
ALDH1
Erythropoietin
Protein kinase B
Cell Proliferation
Settore MED/04 - Patologia Generale
Chemotherapy
business.industry
MORTALITY
Cancer
RECOMBINANT-HUMAN-ERYTHROPOIETIN
medicine.disease
ALPHA
Tumor progression
Inbred NOD
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c1900337b6678fc86345e983f0593503