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Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model
BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318978/ https://www.ncbi.nlm.nih.gov/pubmed/28103615 http://dx.doi.org/10.1038/bjc.2016.448 |
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author | Bouchard, Gina Therriault, Hélène Geha, Sameh Bujold, Rachel Saucier, Caroline Paquette, Benoit |
author_facet | Bouchard, Gina Therriault, Hélène Geha, Sameh Bujold, Rachel Saucier, Caroline Paquette, Benoit |
author_sort | Bouchard, Gina |
collection | PubMed |
description | BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine whether the expression of the cell membrane protease MT1-MMP in cancer cells was associated with radiation-stimulated development of lung metastases. METHODS: Using invasion chambers, irradiated fibroblasts were used as chemoattractants to assess the invasiveness of TNBC D2A1 cell lines showing downregulated expression of MT1-MMP, which were compared with D2A1-wt (wild-type) and D2A1 shMT1-mock (empty vector) cell lines. In a mouse model, a mammary gland was irradiated followed by the implantation of the downregulated MT1-MMP D2A1, D2A1-wt or D2A1 shMT1-mock cell lines. Migration of D2A1 cells in the mammary gland, number of circulating tumour cells and development of lung metastases were assessed. RESULTS: The reduction of MT1-MMP expression decreased the invasiveness of D2A1 cells and blocked the radiation enhancement of cancer cell invasion. In BALB/c mice, irradiation of the mammary gland has stimulated the invasion of cancer cells, which was associated with a higher number of circulating tumour cells and of lung metastases. These adverse effects of radiation were prevented by downregulating the MT1-MMP. CONCLUSIONS: This study shows that the MT1-MMP is necessary for the radiation enhancement of lung metastasis development, and that its expression level and/or localisation could be evaluated as a biomarker for predicting the early recurrence observed in some TNBC patients. |
format | Online Article Text |
id | pubmed-5318978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53189782018-02-14 Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model Bouchard, Gina Therriault, Hélène Geha, Sameh Bujold, Rachel Saucier, Caroline Paquette, Benoit Br J Cancer Translational Therapeutics BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine whether the expression of the cell membrane protease MT1-MMP in cancer cells was associated with radiation-stimulated development of lung metastases. METHODS: Using invasion chambers, irradiated fibroblasts were used as chemoattractants to assess the invasiveness of TNBC D2A1 cell lines showing downregulated expression of MT1-MMP, which were compared with D2A1-wt (wild-type) and D2A1 shMT1-mock (empty vector) cell lines. In a mouse model, a mammary gland was irradiated followed by the implantation of the downregulated MT1-MMP D2A1, D2A1-wt or D2A1 shMT1-mock cell lines. Migration of D2A1 cells in the mammary gland, number of circulating tumour cells and development of lung metastases were assessed. RESULTS: The reduction of MT1-MMP expression decreased the invasiveness of D2A1 cells and blocked the radiation enhancement of cancer cell invasion. In BALB/c mice, irradiation of the mammary gland has stimulated the invasion of cancer cells, which was associated with a higher number of circulating tumour cells and of lung metastases. These adverse effects of radiation were prevented by downregulating the MT1-MMP. CONCLUSIONS: This study shows that the MT1-MMP is necessary for the radiation enhancement of lung metastasis development, and that its expression level and/or localisation could be evaluated as a biomarker for predicting the early recurrence observed in some TNBC patients. Nature Publishing Group 2017-02-14 2017-01-19 /pmc/articles/PMC5318978/ /pubmed/28103615 http://dx.doi.org/10.1038/bjc.2016.448 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Translational Therapeutics Bouchard, Gina Therriault, Hélène Geha, Sameh Bujold, Rachel Saucier, Caroline Paquette, Benoit Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model |
title | Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model |
title_full | Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model |
title_fullStr | Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model |
title_full_unstemmed | Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model |
title_short | Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model |
title_sort | radiation-induced lung metastasis development is mt1-mmp-dependent in a triple-negative breast cancer mouse model |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318978/ https://www.ncbi.nlm.nih.gov/pubmed/28103615 http://dx.doi.org/10.1038/bjc.2016.448 |
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