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
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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