Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal Academic Article uri icon

Overview

MeSH Major

  • Breast Neoplasms
  • Erythropoietin
  • Neoplastic Stem Cells

abstract

  • Erythropoietin (EPO) is a hormone that induces red blood cell production. In its recombinant form, EPO is the one of most prescribed drugs to treat anemia, including that arising in cancer patients. In randomized trials, EPO administration to cancer patients has been associated with decreased survival. Here, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer, we found that EPO promoted tumorigenesis by activating JAK/STAT signaling in breast tumor-initiating cells (TICs) and promoted TIC self renewal. We determined that EPO was induced by hypoxia in breast cancer cell lines, but not in human mammary epithelial cells. Additionally, we demonstrated that high levels of endogenous EPO gene expression correlated with shortened relapse-free survival and that pharmacologic JAK2 inhibition was synergistic with chemotherapy for tumor growth inhibition in vivo. These data define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and reveal a potential application of EPO pathway inhibition in breast cancer therapy.

publication date

  • February 3, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3904607

Digital Object Identifier (DOI)

  • 10.1172/JCI69804

PubMed ID

  • 24435044

Additional Document Info

start page

  • 553

end page

  • 63

volume

  • 124

number

  • 2