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The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts
Metastatic bone disease has a major impact on morbidity of breast cancer (BC) patients. Alterations in mTOR signaling are involved both in cancer progression and in osteoclast differentiation. The purpose of this study was to assess the role of mTOR inhibitor Everolimus (Eve) on osteoclastogenesis i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133828/ https://www.ncbi.nlm.nih.gov/pubmed/27809291 http://dx.doi.org/10.3390/ijms17111827 |
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author | Mercatali, Laura Spadazzi, Chiara Miserocchi, Giacomo Liverani, Chiara De Vita, Alessandro Bongiovanni, Alberto Recine, Federica Amadori, Dino Ibrahim, Toni |
author_facet | Mercatali, Laura Spadazzi, Chiara Miserocchi, Giacomo Liverani, Chiara De Vita, Alessandro Bongiovanni, Alberto Recine, Federica Amadori, Dino Ibrahim, Toni |
author_sort | Mercatali, Laura |
collection | PubMed |
description | Metastatic bone disease has a major impact on morbidity of breast cancer (BC) patients. Alterations in mTOR signaling are involved both in cancer progression and in osteoclast differentiation. The purpose of this study was to assess the role of mTOR inhibitor Everolimus (Eve) on osteoclastogenesis induced by triple negative BC cells. To this aim, we developed an in vitro human model of osteoclastogenesis from peripheral blood monocytes co-cultured with the triple negative SCP2 and the hormonal receptor positive MCF7 cell lines. Osteoclastogenesis was evaluated by TRAP staining, evaluation of F actin rings and Calcitonin Receptor expression. Eve significantly reduced differentiation induced by cancer cells and resulted more effective when evaluated in combination with Denosumab and Zoledronic Acid (Zol). Combination with Zol showed a total abrogation of osteoclast differentiation induced by the triple negative cell line, not by MCF7. Finally, we observed that Eve was active in the inhibition of the crosstalk between cancer cells and osteoclasts reproduced by our model, highlighting a new therapeutic choice for the subsetting of triple negative BC patients. We observed a difference in the response to bone-targeted therapy with respect to BC subtypes. Our model may represent a valid platform for preclinical trials on bone-targeted drugs and for the study of the interplay of BC with bone stromal cells. |
format | Online Article Text |
id | pubmed-5133828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-51338282016-12-12 The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts Mercatali, Laura Spadazzi, Chiara Miserocchi, Giacomo Liverani, Chiara De Vita, Alessandro Bongiovanni, Alberto Recine, Federica Amadori, Dino Ibrahim, Toni Int J Mol Sci Article Metastatic bone disease has a major impact on morbidity of breast cancer (BC) patients. Alterations in mTOR signaling are involved both in cancer progression and in osteoclast differentiation. The purpose of this study was to assess the role of mTOR inhibitor Everolimus (Eve) on osteoclastogenesis induced by triple negative BC cells. To this aim, we developed an in vitro human model of osteoclastogenesis from peripheral blood monocytes co-cultured with the triple negative SCP2 and the hormonal receptor positive MCF7 cell lines. Osteoclastogenesis was evaluated by TRAP staining, evaluation of F actin rings and Calcitonin Receptor expression. Eve significantly reduced differentiation induced by cancer cells and resulted more effective when evaluated in combination with Denosumab and Zoledronic Acid (Zol). Combination with Zol showed a total abrogation of osteoclast differentiation induced by the triple negative cell line, not by MCF7. Finally, we observed that Eve was active in the inhibition of the crosstalk between cancer cells and osteoclasts reproduced by our model, highlighting a new therapeutic choice for the subsetting of triple negative BC patients. We observed a difference in the response to bone-targeted therapy with respect to BC subtypes. Our model may represent a valid platform for preclinical trials on bone-targeted drugs and for the study of the interplay of BC with bone stromal cells. MDPI 2016-11-01 /pmc/articles/PMC5133828/ /pubmed/27809291 http://dx.doi.org/10.3390/ijms17111827 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mercatali, Laura Spadazzi, Chiara Miserocchi, Giacomo Liverani, Chiara De Vita, Alessandro Bongiovanni, Alberto Recine, Federica Amadori, Dino Ibrahim, Toni The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts |
title | The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts |
title_full | The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts |
title_fullStr | The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts |
title_full_unstemmed | The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts |
title_short | The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts |
title_sort | effect of everolimus in an in vitro model of triple negative breast cancer and osteoclasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133828/ https://www.ncbi.nlm.nih.gov/pubmed/27809291 http://dx.doi.org/10.3390/ijms17111827 |
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