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Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077318/ https://www.ncbi.nlm.nih.gov/pubmed/24770893 http://dx.doi.org/10.1007/s00441-014-1823-y |
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author | Hattermann, Kirsten Holzenburg, Eric Hans, Friederike Lucius, Ralph Held-Feindt, Janka Mentlein, Rolf |
author_facet | Hattermann, Kirsten Holzenburg, Eric Hans, Friederike Lucius, Ralph Held-Feindt, Janka Mentlein, Rolf |
author_sort | Hattermann, Kirsten |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00441-014-1823-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4077318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-40773182014-07-25 Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells Hattermann, Kirsten Holzenburg, Eric Hans, Friederike Lucius, Ralph Held-Feindt, Janka Mentlein, Rolf Cell Tissue Res Regular Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00441-014-1823-y) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2014-04-26 2014 /pmc/articles/PMC4077318/ /pubmed/24770893 http://dx.doi.org/10.1007/s00441-014-1823-y Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License, which permits any use, distribution and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Regular Article Hattermann, Kirsten Holzenburg, Eric Hans, Friederike Lucius, Ralph Held-Feindt, Janka Mentlein, Rolf Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells |
title | Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells |
title_full | Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells |
title_fullStr | Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells |
title_full_unstemmed | Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells |
title_short | Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells |
title_sort | effects of the chemokine cxcl12 and combined internalization of its receptors cxcr4 and cxcr7 in human mcf-7 breast cancer cells |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077318/ https://www.ncbi.nlm.nih.gov/pubmed/24770893 http://dx.doi.org/10.1007/s00441-014-1823-y |
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