Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model

Pavlou, M; Shah, M; Gikas, P; Briggs, T; Roberts, S J; Cheema, U

Abstract

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 focussed 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 

Citation

Pavlou, M., Shah, M., Gikas, P., Briggs, T., Roberts, S. J., & Cheema, U. (in press). Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model. Acta Biomaterialia, 96, 247-257. https://doi.org/10.1016/j.actbio.2019.07.011

• Journal Article Type: Article
• Acceptance Date: Jul 9, 2019
• Deposit Date: Aug 6, 2019
• Publicly Available Date: Nov 20, 2020
• Journal: Acta Biomaterialia
• Print ISSN: 1742-7061
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 96
• Pages: 247-257
• DOI: https://doi.org/10.1016/j.actbio.2019.07.011
• Public URL: https://rvc-repository.worktribe.com/output/1381316