Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells.
Cell Tissue Res
; 357(1): 253-66, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24770893
ABSTRACT
The chemokine CXCL12 (stromal cell-derived factor-1, SDF-1) and its receptor CXCR4 play a major role in tumor initiation, promotion, progression and metastasis, especially for breast cancer cells. Recently, CXCR7 has been identified as a second receptor for CXCL12; nevertheless, it also binds CXCL11 (interferon-inducible T cell α chemoattractant, I-TAC). However, little is known about the co-expression of the two receptors and their interactions. Quantitative reverse transcription plus the polymerase chain reaction has demonstrated that both receptors are frequently co-expressed in breast cancer cell lines, whereas other tumor cell lines often express only one of them. For interaction studies, we chose MCF-7 breast cancer cells, since they highly express CXCR4 and CXCR7 at the protein level but not CXCR3 (another target for CXCL11). Immunofluorescence and gold-labeling by light and electron microscopy, respectively, revealed that both receptors were localized at the cell surface in non-stimulated cells. After exposure to CXCL12 or CXCL11, the receptors were rapidly internalized alone or in close proximity. Stimulation with the CXCR4- or CXCR7-selective non-peptide antagonists AMD3100 and CCX733 resulted not only in single internalization but partly also in co-internalization of the two receptors. Furthermore, both chemokine ligands reduced staurosporine-induced apoptosis and caspase-3/7 activation; however, the selective inhibitors merely had partial inhibitory effects on these biological responses. Our findings suggest that CXCR4 and CXCR7 closely interact in breast cancer cells. Both are co-internalized, transduce signals and induce further biological effects partly independently of a selective stimulus or antagonist.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptores CXCR4
/
Quimiocina CXCL12
/
Receptores CXCR
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell Tissue Res
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha