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Int. J. Mol. Sci. 2016, 17(11), 1827;

The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts

Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
The authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Maria Alfonsina Desiderio
Received: 30 June 2016 / Revised: 21 October 2016 / Accepted: 27 October 2016 / Published: 1 November 2016
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Bone Metastasis)
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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. View Full-Text
Keywords: breast cancer; bone metastasis; everolimus; triple negative breast cancer; bone metastasis; everolimus; triple negative

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mercatali, L.; Spadazzi, C.; Miserocchi, G.; Liverani, C.; De Vita, A.; Bongiovanni, A.; Recine, F.; Amadori, D.; Ibrahim, T. The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts. Int. J. Mol. Sci. 2016, 17, 1827.

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