Research Papers:

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells

Francesca Salamanna, Veronica Borsari _, Silvia Brogini, Gianluca Giavaresi, Annapaola Parrilli, Simona Cepollaro, Matteo Cadossi, Lucia Martini, Antonio Mazzotti and Milena Fini

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Oncotarget. 2016; 7:76966-76983. https://doi.org/10.18632/oncotarget.12763

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Francesca Salamanna1,2, Veronica Borsari1, Silvia Brogini2, Gianluca Giavaresi1,3, Annapaola Parrilli1, Simona Cepollaro2,4, Matteo Cadossi5,6, Lucia Martini1,2, Antonio Mazzotti5,6, Milena Fini1,2

1Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy

2Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy

3Laboratory of Tissue Engineering-Innovative Technology Platforms for Tissue Engineering, Rizzoli Orthopedic Institute, Palermo, Italy

4Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

5I Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

6University of Bologna, Bologna, Italy

Correspondence to:

Veronica Borsari, email: [email protected]

Keywords: 3D model, cancer-bone metastasis model, human bone tissue, human sex-related cancer cells

Received: November 02, 2015     Accepted: September 27, 2016     Published: October 19, 2016


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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