A1 Refereed original research article in a scientific journal
Modelling stromal compartments to recapitulate the ameloblastoma tumour microenvironment
Authors: Bakkalci Deniz, Zubir Amir Zaki Abdullah, Khurram Syed Ali, Pape Judith, Heikinheimo Kristiina, Fedele Stefano, Cheema Umber
Publisher: Elsevier
Publication year: 2022
Journal: Matrix biology plus
Journal name in source: Matrix biology plus
Journal acronym: Matrix Biol Plus
Article number: 100125
Volume: 16
ISSN: 2590-0285
eISSN: 2590-0285
DOI: https://doi.org/10.1016/j.mbplus.2022.100125
Web address : https://doi.org/10.1016/j.mbplus.2022.100125
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/177775892
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.
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