CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts

Recent evidence suggests that breast cancer and other solid tumors possess a rare population of cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. We report here the development of a strategy to target these breast cancer stem cells (CSCs) through blockade of the IL-8 receptor CXCR1. CXCR1 blockade using either a CXCR1-specific blocking antibody or repertaxin, a small-molecule CXCR1 inhibitor, selectively depleted the CSC population in 2 human breast cancer cell lines in vitro. Furthermore, this was followed by the induction of massive apoptosis in the bulk tumor population via FASL/FAS signaling. The effects of CXCR1 blockade on CSC viability and on FASL production…

• UO
  University of Michigan
• AA
  A. Alfred Taubman Medical Research Institute
• IN
  Institut National de la Santé et de la Recherche Médicale
• IN
  Institut National Du Cancer
• NI
  National Institutes of Health

  Awards: CA101860, 5P30CA46592
• DD
  Direction de l’hospitalisation et de l’offre de Soins