The Effect of Everolimus in an In Vitro Model of Triple Negative Breast Cancer and Osteoclasts
Autor: | Laura Mercatali, Dino Amadori, Federica Recine, Toni Ibrahim, Chiara Spadazzi, Alberto Bongiovanni, Alessandro De Vita, Giacomo Miserocchi, Chiara Liverani |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Gene Expression Osteoclasts Triple Negative Breast Neoplasms Zoledronic Acid lcsh:Chemistry 0302 clinical medicine Transforming Growth Factor beta Osteonectin Calcitonin receptor lcsh:QH301-705.5 Spectroscopy Triple-negative breast cancer Cells Cultured bone metastasis Diphosphonates Reverse Transcriptase Polymerase Chain Reaction Imidazoles Bone metastasis Cell Differentiation General Medicine Intercellular Adhesion Molecule-1 Computer Science Applications medicine.anatomical_structure Denosumab 030220 oncology & carcinogenesis MCF-7 Cells medicine.drug Receptors CXCR4 Stromal cell Blotting Western Antineoplastic Agents Bone Neoplasms Models Biological Catalysis Article triple negative Inorganic Chemistry 03 medical and health sciences Breast cancer breast cancer everolimus Osteoclast Cell Line Tumor medicine Humans Everolimus Physical and Theoretical Chemistry Molecular Biology business.industry Interleukin-6 Organic Chemistry RANK Ligand medicine.disease Coculture Techniques 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Cancer cell Immunology Cancer research business Biomarkers |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 17, Iss 11, p 1827 (2016) International Journal of Molecular Sciences; Volume 17; Issue 11; Pages: 1827 |
ISSN: | 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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