Pavlou, M;
Shah, M;
Gikas, P;
Briggs, T;
Roberts, SJ;
Cheema, U;
Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model.
Acta Biomaterialia
10.1016/j.actbio.2019.07.011.
(In press).
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Abstract
Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for personalised treatment is a promising approach to address this issue. This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its surrounding. Although the tumour microenvironment impacts osteosarcoma in many ways, this model was focused on interrogating the influence of a biomimetic matrix on tumour cell behaviour. The 3D matrix was supplemented with the bone-marrow proteins laminin, fibronectin and NuOss® bone granules. This led to increased invasion of osteosarcoma cell aggregates from within the bone-like matrix into the surrounding acellular bone-marrow-like ECM. The presence of bone granules also yielded an atypical molecular profile of osteosarcoma cells, suggesting malignant metabolic reprogramming. Changes include decreased MMP-9 (p<0.05) and increased PTEN (p<0.05), MCP-1 (p<0.01) and MCT-4 (p<0.05) gene expression. This complex 3D biomimetic composition also changed cellular responses to doxorubicin, a common chemotherapeutic agent used to treat osteosarcoma, and reproduced key issues of in vivo treatment like drug penetrance and doxorubicin-induced bone toxicity. This work highlights the impact of a biomimetic matrix in 3D osteosarcoma models for both basic and translational research.
| Type: | Article |
|---|---|
| Title: | Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.actbio.2019.07.011 |
| Publisher version: | https://doi.org/10.1016/j.actbio.2019.07.011 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
| Keywords: | 3D model; tumour engineering; osteosarcoma niche; biomimetic; doxorubicin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10077995 |
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