Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Mercatali, Laura, Spadazzi, Chiara, Miserocchi, Giacomo, Liverani, Chiara, De Vita, Alessandro, Bongiovanni, Alberto, Recine, Federica, Amadori, Dino, Ibrahim, Toni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
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
_version_ 1782471347541114880
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
work_keys_str_mv AT mercatalilaura theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT spadazzichiara theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT miserocchigiacomo theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT liveranichiara theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT devitaalessandro theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT bongiovannialberto theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT recinefederica theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT amadoridino theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT ibrahimtoni theeffectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT mercatalilaura effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT spadazzichiara effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT miserocchigiacomo effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT liveranichiara effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT devitaalessandro effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT bongiovannialberto effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT recinefederica effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT amadoridino effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts
AT ibrahimtoni effectofeverolimusinaninvitromodeloftriplenegativebreastcancerandosteoclasts