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CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors
BACKGROUND: The receptor CXCR4 and its ligand CXCL12 play crucial roles in breast cancer. Despite the fact that the spontaneous feline mammary carcinoma (FMC) is considered a suitable model for breast cancer studies, the importance of the CXCR4/CXCL12 axis in FMC is completely unknown. Therefore, th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048851/ https://www.ncbi.nlm.nih.gov/pubmed/30012106 http://dx.doi.org/10.1186/s12885-018-4650-9 |
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author | Marques, Cláudia S. Santos, Ana Rita Gameiro, Andreia Correia, Jorge Ferreira, Fernando |
author_facet | Marques, Cláudia S. Santos, Ana Rita Gameiro, Andreia Correia, Jorge Ferreira, Fernando |
author_sort | Marques, Cláudia S. |
collection | PubMed |
description | BACKGROUND: The receptor CXCR4 and its ligand CXCL12 play crucial roles in breast cancer. Despite the fact that the spontaneous feline mammary carcinoma (FMC) is considered a suitable model for breast cancer studies, the importance of the CXCR4/CXCL12 axis in FMC is completely unknown. Therefore, this work aims to elucidate the role of CXCR4 and its ligand in the progression of FMC and metastatic disease. METHODS: CXCR4 and CXCL12 expression was analyzed by immunohistochemistry and immunofluorescence on primary tumors (PT), regional and distant metastases of female cats with mammary carcinoma and correlated with serum CXCL12 levels, tumor molecular subtypes and clinicopathological features. RESULTS: CXCR4 was more expressed in PT than in metastases (p = 0.0067), whereas CXCL12 was highly expressed in metastatic lesions located in liver and lung (p < 0.0001), as reported for human breast cancer. Moreover, cats with CXCR4 positive PT exhibited significantly lower serum CXCL12 levels than cats with CXCR4 negative mammary carcinomas (p = 0.0324). At metastatic lesions, HER2-overexpressing tumors presented higher CXCR4 expression than the other molecular tumor subtypes (p = 0.012) and significant differences in overall (p = 0.0147) and disease-free survival (p = 0.0279) curves between the cats with CXCL12 positive and CXCL12 negative tumors were found. Indeed, CXCL12 negative PT were associated with unfavorable prognosis in cats with HER2-overexpressing tumors. CONCLUSIONS: This work exposes part of the complex interaction between CXCR4 and CXCL12 in PT, but also in metastases of a breast cancer model. These findings could uncover novel therapeutic tools to be used in cats and humans. |
format | Online Article Text |
id | pubmed-6048851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60488512018-07-19 CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors Marques, Cláudia S. Santos, Ana Rita Gameiro, Andreia Correia, Jorge Ferreira, Fernando BMC Cancer Research Article BACKGROUND: The receptor CXCR4 and its ligand CXCL12 play crucial roles in breast cancer. Despite the fact that the spontaneous feline mammary carcinoma (FMC) is considered a suitable model for breast cancer studies, the importance of the CXCR4/CXCL12 axis in FMC is completely unknown. Therefore, this work aims to elucidate the role of CXCR4 and its ligand in the progression of FMC and metastatic disease. METHODS: CXCR4 and CXCL12 expression was analyzed by immunohistochemistry and immunofluorescence on primary tumors (PT), regional and distant metastases of female cats with mammary carcinoma and correlated with serum CXCL12 levels, tumor molecular subtypes and clinicopathological features. RESULTS: CXCR4 was more expressed in PT than in metastases (p = 0.0067), whereas CXCL12 was highly expressed in metastatic lesions located in liver and lung (p < 0.0001), as reported for human breast cancer. Moreover, cats with CXCR4 positive PT exhibited significantly lower serum CXCL12 levels than cats with CXCR4 negative mammary carcinomas (p = 0.0324). At metastatic lesions, HER2-overexpressing tumors presented higher CXCR4 expression than the other molecular tumor subtypes (p = 0.012) and significant differences in overall (p = 0.0147) and disease-free survival (p = 0.0279) curves between the cats with CXCL12 positive and CXCL12 negative tumors were found. Indeed, CXCL12 negative PT were associated with unfavorable prognosis in cats with HER2-overexpressing tumors. CONCLUSIONS: This work exposes part of the complex interaction between CXCR4 and CXCL12 in PT, but also in metastases of a breast cancer model. These findings could uncover novel therapeutic tools to be used in cats and humans. BioMed Central 2018-07-16 /pmc/articles/PMC6048851/ /pubmed/30012106 http://dx.doi.org/10.1186/s12885-018-4650-9 Text en © The Author(s). 2018 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 Marques, Cláudia S. Santos, Ana Rita Gameiro, Andreia Correia, Jorge Ferreira, Fernando CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors |
title | CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors |
title_full | CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors |
title_fullStr | CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors |
title_full_unstemmed | CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors |
title_short | CXCR4 and its ligand CXCL12 display opposite expression profiles in feline mammary metastatic disease, with the exception of HER2-overexpressing tumors |
title_sort | cxcr4 and its ligand cxcl12 display opposite expression profiles in feline mammary metastatic disease, with the exception of her2-overexpressing tumors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048851/ https://www.ncbi.nlm.nih.gov/pubmed/30012106 http://dx.doi.org/10.1186/s12885-018-4650-9 |
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