CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts.
J Clin Invest
; 120(2): 485-97, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-20051626
ABSTRACT
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 were mediated by the FAK/AKT/FOXO3A pathway. In addition, repertaxin was able to specifically target the CSC population in human breast cancer xenografts, retarding tumor growth and reducing metastasis. Our data therefore suggest that CXCR1 blockade may provide a novel means of targeting and eliminating breast CSCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Células-Tronco Neoplásicas
/
Neoplasias da Mama
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Receptores de Interleucina-8A
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos