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CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer

BACKGROUND: Cytokines are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play key role in tumor dissemination and are an independent survival predictor in breast cancer patients. The aim of this study was to assess correlation between CTCs and plasma cytokines in primary...

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Autores principales: Mego, M., Cholujova, D., Minarik, G., Sedlackova, T., Gronesova, P., Karaba, M., Benca, J., Cingelova, S., Cierna, Z., Manasova, D., Pindak, D., Sufliarsky, J., Cristofanilli, M., Reuben, J. M., Mardiak, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759765/
https://www.ncbi.nlm.nih.gov/pubmed/26896000
http://dx.doi.org/10.1186/s12885-016-2143-2
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author Mego, M.
Cholujova, D.
Minarik, G.
Sedlackova, T.
Gronesova, P.
Karaba, M.
Benca, J.
Cingelova, S.
Cierna, Z.
Manasova, D.
Pindak, D.
Sufliarsky, J.
Cristofanilli, M.
Reuben, J. M.
Mardiak, J.
author_facet Mego, M.
Cholujova, D.
Minarik, G.
Sedlackova, T.
Gronesova, P.
Karaba, M.
Benca, J.
Cingelova, S.
Cierna, Z.
Manasova, D.
Pindak, D.
Sufliarsky, J.
Cristofanilli, M.
Reuben, J. M.
Mardiak, J.
author_sort Mego, M.
collection PubMed
description BACKGROUND: Cytokines are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play key role in tumor dissemination and are an independent survival predictor in breast cancer patients. The aim of this study was to assess correlation between CTCs and plasma cytokines in primary breast cancer (PBC) patients. METHODS: This study included 147 chemotherapy naïve PBC patients. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoetic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (Twist1, Snail1, Slug, Zeb1) and epithelial (Ck19) gene transcripts by qRT-PCR. The concentrations of 51 plasma cytokines were measured using multiplex bead arrays. RESULTS: CTCs were detected in 25.2 % patients. CTCs exhibiting only epithelial markers (CTC_EP) and only EMT markers (CTC_EMT) were present evenly in 11.6 % patients, while CTCs co-expressing both markers were detected in 2.0 % patients. Patients with presence of CTC_EP in peripheral blood had significantly elevated levels of plasma IFN-α2, IL-3, MCP-3, β-NGF, SCF, SCGF-β, TNF-β and SDF-1 compared to patients without CTC_EP. CTC_EP exhibited overexpression of SDF-1 receptor and CXCR4, but not other corresponding cytokine receptor, and in multivariate analysis SDF-1 was independently associated with CTC_EP. There was an inverse correlation between CTC_EMT and plasma cytokines CTACK, β-NGF and TRAIL, while presence of either subtype of CTCs was associated with increased level of TGF-β2. CONCLUSION: Using cytokine profiling, we identified cytokines associated with CTCs subpopulations in peripheral blood of PBC. Our data suggest that CXCR4-SDF-1 axis is involved in mobilization and trafficking of epithelial CTCs.
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spelling pubmed-47597652016-02-20 CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer Mego, M. Cholujova, D. Minarik, G. Sedlackova, T. Gronesova, P. Karaba, M. Benca, J. Cingelova, S. Cierna, Z. Manasova, D. Pindak, D. Sufliarsky, J. Cristofanilli, M. Reuben, J. M. Mardiak, J. BMC Cancer Research Article BACKGROUND: Cytokines are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play key role in tumor dissemination and are an independent survival predictor in breast cancer patients. The aim of this study was to assess correlation between CTCs and plasma cytokines in primary breast cancer (PBC) patients. METHODS: This study included 147 chemotherapy naïve PBC patients. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoetic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (Twist1, Snail1, Slug, Zeb1) and epithelial (Ck19) gene transcripts by qRT-PCR. The concentrations of 51 plasma cytokines were measured using multiplex bead arrays. RESULTS: CTCs were detected in 25.2 % patients. CTCs exhibiting only epithelial markers (CTC_EP) and only EMT markers (CTC_EMT) were present evenly in 11.6 % patients, while CTCs co-expressing both markers were detected in 2.0 % patients. Patients with presence of CTC_EP in peripheral blood had significantly elevated levels of plasma IFN-α2, IL-3, MCP-3, β-NGF, SCF, SCGF-β, TNF-β and SDF-1 compared to patients without CTC_EP. CTC_EP exhibited overexpression of SDF-1 receptor and CXCR4, but not other corresponding cytokine receptor, and in multivariate analysis SDF-1 was independently associated with CTC_EP. There was an inverse correlation between CTC_EMT and plasma cytokines CTACK, β-NGF and TRAIL, while presence of either subtype of CTCs was associated with increased level of TGF-β2. CONCLUSION: Using cytokine profiling, we identified cytokines associated with CTCs subpopulations in peripheral blood of PBC. Our data suggest that CXCR4-SDF-1 axis is involved in mobilization and trafficking of epithelial CTCs. BioMed Central 2016-02-19 /pmc/articles/PMC4759765/ /pubmed/26896000 http://dx.doi.org/10.1186/s12885-016-2143-2 Text en © Mego et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mego, M.
Cholujova, D.
Minarik, G.
Sedlackova, T.
Gronesova, P.
Karaba, M.
Benca, J.
Cingelova, S.
Cierna, Z.
Manasova, D.
Pindak, D.
Sufliarsky, J.
Cristofanilli, M.
Reuben, J. M.
Mardiak, J.
CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
title CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
title_full CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
title_fullStr CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
title_full_unstemmed CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
title_short CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
title_sort cxcr4-sdf-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759765/
https://www.ncbi.nlm.nih.gov/pubmed/26896000
http://dx.doi.org/10.1186/s12885-016-2143-2
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