A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

Francesca Salamanna, Deyanira Contartese _, Melania Maglio and Milena Fini

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Oncotarget. 2016; 7:44803-44820. https://doi.org/10.18632/oncotarget.8394

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Francesca Salamanna1, Deyanira Contartese2, Melania Maglio1 and Milena Fini1,2

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

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

Correspondence to:

Deyanira Contartese, email:

Keywords: systematic literature review, bone metastases, 3D in vitro model, cancer cells, metastatic microenvironment

Received: January 20, 2016 Accepted: March 18, 2016 Published: March 26, 2016


While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients’ quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.

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