期刊
ONCOTARGET
卷 7, 期 47, 页码 76966-76983出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12763
关键词
3D model; cancer-bone metastasis model; human bone tissue; human sex-related cancer cells
资金
- Rizzoli Orthopedic Institute (Ricerca Corrente)
- 5 x 1000 Project Sviluppo e validazione di modelli alternativi e complementari in vitro (intelligent testing strategy) in ortopedia e traumatologia
- Operational Programme ERDF in the region Emilia-Romagna: Activity The 1.1 Creation of technology centers for Industrial research and technological transfer
- Project: Tumor microenvironment: potential role of osteoporosis in the development of bone metastases. In vitro and in vivo studies, programma di ricerca Regione-Universita Area 1-Bando Giovani Ricercatori
One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.
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