Modelling stromal compartments to recapitulate the ameloblastoma tumour microenvironment.

Autor: Bakkalci D; UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS London, UK., Zubir AZA; Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, S10 2TA Sheffield, UK., Khurram SA; Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, S10 2TA Sheffield, UK., Pape J; UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS London, UK., Heikinheimo K; Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Turku and Turku University Hospital, Turku, Finland., Fedele S; Eastman Dental Institute, University College London, London, UK., Cheema U; UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS London, UK.
Jazyk: angličtina
Zdroj: Matrix biology plus [Matrix Biol Plus] 2022 Nov 21; Vol. 16, pp. 100125. Date of Electronic Publication: 2022 Nov 21 (Print Publication: 2022).
DOI: 10.1016/j.mbplus.2022.100125
Abstrakt: Tumour development and progression is dependent upon tumour cell interaction with the tissue stroma. Bioengineering the tumour-stroma microenvironment (TME) into 3D biomimetic models is crucial to gain insight into tumour cell development and progression pathways and identify therapeutic targets. Ameloblastoma is a benign but locally aggressive epithelial odontogenic neoplasm that mainly occurs in the jawbone and can cause significant morbidity and sometimes death. The molecular mechanisms for ameloblastoma progression are poorly understood. A spatial model recapitulating the tumour and stroma was engineered to show that without a relevant stromal population, tumour invasion is quantitatively decreased. Where a relevant stroma was engineered in dense collagen populated by gingival fibroblasts, enhanced receptor activator of nuclear factor kappa-B ligand (RANKL) expression was observed and histopathological properties, including ameloblastoma tumour islands, developed and were quantified. Using human osteoblasts (bone stroma) further enhanced the biomimicry of ameloblastoma histopathological phenotypes. This work demonstrates the importance of the two key stromal populations, osteoblasts, and gingival fibroblasts, for accurate 3D biomimetic ameloblastoma modelling.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Crown Copyright © 2022 Published by Elsevier B.V.)
Databáze: MEDLINE